CLINICAL
EMBRYOLOGY

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INDIAN DENTAL ACADEMY
Leader in continuing dental education
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Introduction
• Growth and development of an individual can be
divided into prenatal and the post natal periods.
• The pren...
5 principal stages in craniofacial
development are
• Germ layer formation and initial organization of
craniofacial structu...
The prenatal life can be arbitrarily divided
into 3 periods
• Period of ovum
• Period of embryo
• Period of fetus

www.ind...
Period of ovum
• This period extends approx 2 weeks from
the time of fertilization.
• During this period the cleavage of t...
• Human development begins when a
sperm fertilizes an oocyte resulting in the
formation of zygote.
• The zygote undergoes ...
• A fluid filled space develops within the
morula, called Blastocele and the entire
structure is now known as blasocyst.
•...
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Period of embryo
• This period extends from 14th day to 56th
day of intra uterine life.
• During this period the major par...
• Bilaminar disc comprised of epiblast and
hypoblast .
• The epiblast is made of columnar cells and
separated from cytotro...
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• Early in the third week one more important
structure develops known as notochord,
which is basically formed by the cells...
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Neurilation
• It is the process of development of the neural
plate, neuroectoderm and finally foldings to
produce the neur...
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• Very high levels
of ethanol during
this period causes
deficiency of the
midline tissue of
the neural plate
resulting in
...
Role of neural crest cells in the
facial development
• Development of the face depends not only
on the underlying brain an...
• Fundamental to facial formation is the
differentiation, development and migration
of the secondary germ layer tissue
des...
•The neural crest /neural plate is a transient
structure which can be subdivided into 4
functional domains.
Cranial neural...
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• Neural crest cells originating in the mid
brain and the from the first two
rhombomeres are important in providing
mesenc...
• According to Lumsden and Keynes the hindbrain
is itself is composed of segments with 8 subunits
called as Rhombomeres.
•...
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•During craniofacial development ,neural
crest cells especially CNC cells migrate
ventrolaterally as they produce the
bran...
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Clinical significance:• Thalidomide and isotretinoin have severe
influence on the neural crest migration
which lead to var...
• Neural crest cells migrating from the
rhombomeres express the homeobox
(HOX) genes that were expressed in the
rhombomere...
• HOX genes produce transcription factors
that bind to the DNA of other genes and
regulate the gene expression.
• These ge...
Muscle segment (Msx1,Msx2)
HOMEOBOX GENES

Distalless ( Dlx)
Orthodontical (Otx)
Goosecoid (Gsc)

TRANSCRIPTION
FACTORS

+...
• The expression of HOX genes are
mediated through two main group of
regulatory proteins.
• Growth factor family and the
s...
COTROL AT CELLULAR LEVEL
REGULATORY PROTEINS

GROWTH FACTOR FAMILY
e.g. .FGF,EGF,BMPs,TGFalfa

STEROID/THYROID/RETINOIC
AC...
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Neural crest cells
form the majority
of the facial and
cranial skeleton.
However,
mesodermal cells
also contribute t...
Clinical significance
• Mutation in fibroblast growth factor (FGF)
receptor genes are known to affect the suture
developme...
• Msx-1 and Msx-2 are implicated in craniofacial
development and in particular in the initiation,
developmental position(M...
Vulnerability of neural crest cells
Deficiency of Superoxide dismutase and catalase
enzymes responsible for scavenging fre...
Pathogenesis of treacher collins’ syndrome

Excessive
cell death in
the
trigeminal
ganglion

Underdevlopment
of maxilla an...
Pathogenesis of hemi facial microsomia
Early loss of neural crest cells

Cells migrating to lateral and
lower part of the ...
Period of the fetus
• This phase extends from 56th day of intrauterine life till birth.
• In this period ,accelerated grow...
Development of the oral structures
• Development of face occurs primarily
between 4-8 weeks.
• The growth of the cranial ,...
• there is progressive increase in the size of
the embryonic disc, yet the head and tail
end of the disc remain relatively...
After the
formation of
head fold
the
developing
brain and
the
pericardium
form two
prominent
bulges in
the ventral
aspect ...
• In between these ,there is a depression
called the stomodeum,the floor of which is
formed by the buccopharyngeal
membran...
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The buccopharyngeal membrane begins
to break down at this stage to allow
continuity between pharynx and the
stomodeum (pri...
Remnants of the
buccopharyngeal
membrane are
seen between the
stomodeum and
the pharynx,
separating the
ectodermally and
e...
Early in the
fourth week of
human
development
the cranial and
cervical (neck)
regions make
up
approximately
1/2 of the
emb...
The branchial arches
• Differentiation of the face takes place early
in the prenatal life, specifically between
the 5-7 we...
• Five branchial arches are formed
appearing as rounded, tubular
enlargements and are bounded by the
clefts and grooves th...
By the time that
the anterior
neuropore
closes, the first
and second
pharyngeal
arches are
evident.

. Human Age: 27 days
...
The first, second,
third and fourth
arches are visible
externally. The
sixth arch does
not form an
external
elevation.

ww...
The maxillary and
mandibular
prominences of the first
arch contribute the
upper and lower jaw.
The external ear forms
from...
The regions
between the
pharyngeal arches
are termed
pharyngeal clefts.
The indentation
just dorsal to the
second pharynge...
The clefts that
separate the
pharyngeal
arches on the
external surface
of the embryo
are located
opposite
pharyngeal
pouch...
Closing
membranes,
consisting of
ectoderm,
opposed to
endoderm,
separate the
pharyngeal
clefts from
the pouches.

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Each arch
contains
mesenchyme
that is
derived in
part from
neural crest
and in part
from
mesoderm.
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The pharyngeal
arches are
organized
around blood
vessels that
extend dorsally
from the
developing
heart.

www.indiandental...
illustrates the
relationship of the
developing heart
and aortic sac to
the pharyngeal
arches. The
arches surround
the phar...
Nerve supply

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The first pharyngeal
arch has both a
maxillary and a
mandibular
prominence. Dorsal to
the first arch is an
elevation forme...
Each of the
pharyngeal
arches is
supplied by a
specific cranial
nerve.
The cells that
contribute to the
sensory ganglia
ar...
Epibranchial
placodes are
specialized
regions of
surface
ectoderm, the
cells of which
invaginate to
contribute to the
form...
Derivatives of the pouches and
clefts

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Some of the neural crest cells in
each of the arches become
cartilage.

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Development of the face

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•

The
developing
face is
initially
represented
by the
frontonasal
region, and
the first
pharyngeal
(branchial,
visceral)
...
• The human face is first characterized by an
invagination or the dimple in the surface
ectoderm layer appearing just belo...
• As the oral ectodermal plate meet the
endodermal lining of the gut, the
membrane disintegrate and the continuity
between...
Soon the
mesoderm
covering the
developing brain
proliferates and
forms a downward
projection that
overlaps the upper
part ...
In the inferior
and lateral
portion of the
frontonasal
process,
bilateral localize
area of the
surface
ectoderm
thickens t...
• The growth of the heart affects the
development of the face, not only because
of the importance of the blood supply to i...
• Due to migration and proliferation of neural
crest cells into the pharyngeal arch the paired
structures develop surround...
• Medial and lateral
nasal process are
formed due to
proliferation of
mesenchyme
along the
periphery of nasal
placode.
• T...
• Before the fusion of the medial and lateral
nasal process the nasal pit undergoes
further elongation.
• The raised anter...
• The distance between these two pits
remains constant during these period
however pit themselves increase in height
and l...
• Due to proliferation of underlying
mesenchyme in the max.prominences it
moves medially toward each other and
toward the ...
• This segment is important as it gives rise
to the philtrum, four incisor teeth, alveolar
bone and gingiva surrounding th...
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• The fusion between the medial nasal
process and the maxillary process is a
multi step procedure.

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•Initially there is
contact between
the epithelium
covering medial
border of max.
process and the
lateral border of
the me...
• Upon contact
adhesion of two
epithelial sheets occur
and they become
fused into a single
sheet.
• Then degeneration of
t...
• At the posterior limit of the epithelial fin,
the epithelial sheets split apart and
produces an opening between the nasa...
The medial
nasal
prominences
merge in the
midline to
smooth the
median furrow.

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• Later the nasal cavity enlarges posteriorly
to form a space overlying the entire oral
cavity.
• the oral and nasal cavit...
Development of tongue

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Development of the tongue
• The development of the tongue is of
considerable interest because of its importance
in functio...
• The tongue
arise in the
ventral wall
of the
primitive
oropharynx
from the
inner lining
of the first
four
pharyngeal
arch...
• During the 4th week of i.u life paired lateral
thickenings of mesenchyme appear on the
internal aspect of the first phar...
• The lingual swelling grow and fuse to form
the mucosa of anterior 2/3 of the tongue
• Posterior 1/3 develops from hypo
p...
• Around the 5th week of i.u life, the ventral
aspect of the 2nd 3rd and 4th pharyngeal
arches elevate into an united sing...
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• Around the fused lingual swellings there is
epithelial proliferation into the underlying
mesenchyme takes place. Degener...
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The junction of
the anterior twothirds and
posterior third of
the tongue is at
the terminal
sulcus. The
foramen cecum
is t...
Development of connective tissue
and muscle
• Connective tissue develop from local
mesenchyme
• Tongue muscle develop from...
Development of palate
• The palate begins to develop early in the six
week and the process is completed in 12 week.
• The ...
The medial
nasal
prominences
contribute the
tissues that
will form the
anterior part
of the palate,
the primary
palate
(ci...
• The
secondary
palate
arises from
the paired
lateral
palatine
shelves of
the maxilla
which are
oriented in
a superior
–in...
A frontal
cut
illustrates
that the
tongue is
initially
interposed
between
the
secondary
palatal
shelves.
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• Later the lateral palatine shelves of the
maxilla become elongated and the
tongue becomes relatively smaller and
moves i...
• This allows
the shelves
to become
oriented
horizontally
to
approach
one
another
and to fuse
in the
midline

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• The median palatine raphe is the clinical
remnant of fusion between palatine shelves.
• The lateral palatine process als...
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Fusion of the
palatal
shelves with
each other
and with the
nasal septum
separates the
nasal cavities
from the oval
cavity....
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Pathogenesis of cleft lip and cleft
palate
• This occurs when mesenchymal
connective tissue from different
embryological s...
• Cleft palate is the result of failure of the
lateral palatine process to fuse with each
other ,with the nasal septum or ...
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Further growth of the face:-• Even at this early stage the growth pattern
of the face is downward and forward as it
grows ...
Development of the skull
• The skull is formed by mesenchymal
connective tissue around the developing
brain.

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• The development of the skull is
considered in two componentsNeurocraniumcalvaria and
base of the skull
and derived from
...
Cartilaginous neurocranium
• Consists of several cartilages that fuse and
undergo endochondral ossification to give rise t...
The bone formed by this process are
•
•
•
•
•

Occipital bone
Body of the sphenoid bone
Ethmoid bone
Vomer
Petrous and mas...
Membranous neurocranium
• These arises by the intramembranous ossification of the
mesenchyme around the developing brain.
...
The bones formed by this process are
• Flat bones of calvaria.
• Superior portion of the frontal ,occipital
and parietal b...
viscerocranium
• Includes the facial skeleton arises from the
pharyngeal arches.
Cartilaginous component
-includes middle ...
Development of mandible and TMJ
• The template for the mandible is laid down by
meckle’s cartilage of the first pharyngeal...
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• Secondary cartilage develops at the site of
coronoid and condylar process and at the angle.
• By 11 weeks secondary cart...
9 weeks

16 weeks

24 weeks
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30 weeks
• As the two halves of the mandible continue to
grow fibrous connective tissue known as
symphyseal cartilage unite the two...
• Forward growth

Backward
growth

height

Deposition of new
bone along the
anterior surface of
the mandible
Accretion alo...
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Development of maxilla
• A primary intramembranous ossification
center appear for each maxilla in the 8 th
week IU at the ...
Prenatal changing relationship between
maxilla and mandible
• During intra uterine development, the
relative size of the m...
• At about 8 weeks post conception, the maxilla
overlaps the mandible. subsequently the
mandible grows more rapidly, equal...
Clinical significance
•Fibroblast growth factor (FGFs) and fibroblast
growth factor receptors (FGFRs) play a important
rol...
FGFR-1
FGFR-2
FGFR-3

Osteogenic
differentiation
+
+

proliferation
Unclear role

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mutation cr...
• Crnioschisis
(anencephaly)

crniosynostosis

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acrocephaly

scaphocephaly

plagiocephaly
The fetal period—3—9 month
• Craniofacial changes—by the 3rd month face
assumes more human appearance.
• During the fetal ...
• At birth the cranial vault is approx.8times larger
than the face.
• In the embryonic period the cranium to face ratio
ma...
Development of teeth
• By the 7th week, the epithelial labial lamina
develops on the perimeter of the max. and the
mand. p...
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Molecular regulation of tooth
development
• Tooth development represents a classic
example of epithelium and neural crest ...
Development of the salivary gland
• All three major glands develop during 6—8
weeks due to proliferation of the oral mucos...
conclusion
• The clinician’s requirement of the anticipated endpoint of
growth and development of the face to determine
wh...
References:--• Geoffry H.Sperber—New insights in facial
development—Seminar in orthodontics,March
2006,vol-12,no-1,page,4-...
• Vinod Krishnan---Genomics and orofacial clefts-J Ind Orthod Soc 2003,vol--36,page no.39—51.
• Graham A ,Okabe M et al—th...
• Tapadia MD,Cordero DR et al—It’s all in your
head;new insights into craniofacial development
and deformation-- Journal o...
• Williams R.Proffit----Contemporary orthodontics
—3rd edition.St.Louis,CV Mosby,2005.page.6393.
• Sadler TW;-- Langman’s ...
• P.A.Mossey —The heritability of
malocclusion.part-1---Genetics principles and
terminology—BJO 1999 June,vol.26,page.103—...
• Jiang X et al-Tissue origins and interactions in
the mammalian skull vault—Dev.Biol 2002 ,vol206.page-106-11.
• Cavazzan...
www.indiandentalacademy.com
Leader in continuing dental education

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Clinical embryology /certified fixed orthodontic courses by Indian dental academy

  1. 1. CLINICAL EMBRYOLOGY www.indiandentalacademy.com
  2. 2. INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
  3. 3. Introduction • Growth and development of an individual can be divided into prenatal and the post natal periods. • The prenatal period of development is a dynamic phase in the development of a human being. • During this period the height increases by almost 5000 times as compared to only three fold increase during post natal period. www.indiandentalacademy.com
  4. 4. 5 principal stages in craniofacial development are • Germ layer formation and initial organization of craniofacial structures. • Neural tube formation and initial formation of the oropharynx • Origins ,migration and interactions of cell population, especially neural crest cells • Formation of organ system especially the pharyngeal arches and primary and secondary palate • Final differentiation of tissue . www.indiandentalacademy.com
  5. 5. The prenatal life can be arbitrarily divided into 3 periods • Period of ovum • Period of embryo • Period of fetus www.indiandentalacademy.com
  6. 6. Period of ovum • This period extends approx 2 weeks from the time of fertilization. • During this period the cleavage of the ovum and the attachment of the ovum to the intra uterine wall occurs. www.indiandentalacademy.com
  7. 7. • Human development begins when a sperm fertilizes an oocyte resulting in the formation of zygote. • The zygote undergoes cleavage, a series of mitotic divisions as it moves along the uterine tube towards the uterus. • Due to continuous cleavage it turns into a ball of cells when it enters the uterus after 3 days of fertilization, known as morula. www.indiandentalacademy.com
  8. 8. • A fluid filled space develops within the morula, called Blastocele and the entire structure is now known as blasocyst. • At the end of first week and beginning of second week after the fertilization, blastocyst adheres to the surface of the endometrium and implantation begins and inner cell mass forms a bilaminar disc. www.indiandentalacademy.com
  9. 9. www.indiandentalacademy.com
  10. 10. Period of embryo • This period extends from 14th day to 56th day of intra uterine life. • During this period the major part of the facial and the cranial region develops. www.indiandentalacademy.com
  11. 11. • Bilaminar disc comprised of epiblast and hypoblast . • The epiblast is made of columnar cells and separated from cytotrophoblast by a space called amniotic cavity. • During the 3rd week,gastrulation phase, a narrow trough with slightly bulging sides develops in the midline of the epiblast known as primitive streak. • During this stage only epiblast cells migrate in the primitive streak and forms all the three germ layers. www.indiandentalacademy.com
  12. 12. www.indiandentalacademy.com
  13. 13. www.indiandentalacademy.com
  14. 14. • Early in the third week one more important structure develops known as notochord, which is basically formed by the cells in primitive node and pits which proliferate towards cranial end until they reach prechordal plate, which is the future buccopharyngeal membrane. www.indiandentalacademy.com
  15. 15. www.indiandentalacademy.com
  16. 16. Neurilation • It is the process of development of the neural plate, neuroectoderm and finally foldings to produce the neural tube. • Neural tube is the primordium of the central nervous system. • The anterior region of the neural tube enlarges to form the forebrain,midbrain,and the hind brain. • Eight bulges develop in the hind brain known as rhombomeres. Each specific rhombomere give rise to specific neural crest cells which migrate to a specific location. www.indiandentalacademy.com
  17. 17. www.indiandentalacademy.com
  18. 18. • Very high levels of ethanol during this period causes deficiency of the midline tissue of the neural plate resulting in maxillary and mandibular deficiency, known as fetal alcohol syndrome. www.indiandentalacademy.com
  19. 19. Role of neural crest cells in the facial development • Development of the face depends not only on the underlying brain and its subdivisions of prosencephalon,mesencephalon, and rhombencephalon but also on the adjacent secondary neural crest tissue arising from the dorsal margins of the neural folds at a very early stage of embryogenesis. www.indiandentalacademy.com
  20. 20. • Fundamental to facial formation is the differentiation, development and migration of the secondary germ layer tissue designated neural crest ectomesenchyme. • This transitory pleuripotent tissue arises from the lateral marginal crests of the neural primordium and undergoes an epithelio-mesenchymal transition. www.indiandentalacademy.com
  21. 21. •The neural crest /neural plate is a transient structure which can be subdivided into 4 functional domains. Cranial neural crest –give rise to various structure of chondrocranium Trunk neural crest —melanocytes and dorsal root ganglion Vagal and sacral neural crest ---parasympathetic ganglia of gut Cardiac neural crest —melanocytes ,neurons and connective tissue. www.indiandentalacademy.com
  22. 22. www.indiandentalacademy.com
  23. 23. • Neural crest cells originating in the mid brain and the from the first two rhombomeres are important in providing mesenchyme needed for development of face ,first pharyngeal arches structure . www.indiandentalacademy.com
  24. 24. • According to Lumsden and Keynes the hindbrain is itself is composed of segments with 8 subunits called as Rhombomeres. • Neural crest cells destined to 1st branchial arch migrate from the rhombomere 1 and 2 and those for 2 and 3 arches migrate from the rhombomeres 4 and 6,7 respectively. • Neural crest cells from R8 migrate to 4 and 6 arches. • Most of the cells of R3 and R5 undergo cell death by apoptosis • The even no. rhombomeres contain exit point for cranial nerves V,VII and IX which will innervate the branchial arches 1 ,2 and 3. www.indiandentalacademy.com
  25. 25. www.indiandentalacademy.com
  26. 26. •During craniofacial development ,neural crest cells especially CNC cells migrate ventrolaterally as they produce the branchial arches. www.indiandentalacademy.com
  27. 27. www.indiandentalacademy.com
  28. 28. Clinical significance:• Thalidomide and isotretinoin have severe influence on the neural crest migration which lead to various craniofacial malformation. www.indiandentalacademy.com
  29. 29. • Neural crest cells migrating from the rhombomeres express the homeobox (HOX) genes that were expressed in the rhombomeres of origin. www.indiandentalacademy.com
  30. 30. • HOX genes produce transcription factors that bind to the DNA of other genes and regulate the gene expression. • These genes are important in determining the identity and spatial arrangements of body regions and they also help to determine the pattern and positions of structures developing within the pharyngeal arch. www.indiandentalacademy.com
  31. 31. Muscle segment (Msx1,Msx2) HOMEOBOX GENES Distalless ( Dlx) Orthodontical (Otx) Goosecoid (Gsc) TRANSCRIPTION FACTORS + Sonic hedgehog (Shh) - TRNSCRIPTION DNA RNA www.indiandentalacademy.com
  32. 32. • The expression of HOX genes are mediated through two main group of regulatory proteins. • Growth factor family and the steroid/thyroid/retinoic acid super family. www.indiandentalacademy.com
  33. 33. COTROL AT CELLULAR LEVEL REGULATORY PROTEINS GROWTH FACTOR FAMILY e.g. .FGF,EGF,BMPs,TGFalfa STEROID/THYROID/RETINOIC ACID SUPER FAMIILY These are the vehicles through which homeobox genes information is expressed in the coordination of cell migration and subsequent cell interactions that regulate the growth. www.indiandentalacademy.com
  34. 34. www.indiandentalacademy.com
  35. 35.      Neural crest cells form the majority of the facial and cranial skeleton. However, mesodermal cells also contribute to the cranium. www.indiandentalacademy.com
  36. 36. Clinical significance • Mutation in fibroblast growth factor (FGF) receptor genes are known to affect the suture development in humans and such mutations have been found to occur in Apert and Crouzon syndrome. • In suture formation the FGF is thought to provide a signal from the duramater preventing the cells from undergoing premature ossification at presumptive sutures and the FGF receptor mutation disrupts these progenitor osteoblast cells to differentiate and causes fusion to occur prematurely. www.indiandentalacademy.com
  37. 37. • Msx-1 and Msx-2 are implicated in craniofacial development and in particular in the initiation, developmental position(Msx-1) and further development(Msx-2) of the tooth buds. • Bone morphogenetic proteins (BMPs) have been found to have multiple roles not only in bone morphogenesis(BMP-5) but appear to induce dentinogenesis(BMP-7) also. • The mutation in the Msx gene have been reported to be associated with hypodontia. www.indiandentalacademy.com
  38. 38. Vulnerability of neural crest cells Deficiency of Superoxide dismutase and catalase enzymes responsible for scavenging free radicals that damage cells Exposure of teratogenic compounds such as alcohol and retinoic acid Cell death www.indiandentalacademy.com
  39. 39. Pathogenesis of treacher collins’ syndrome Excessive cell death in the trigeminal ganglion Underdevlopment of maxilla and mandible Altered neural crest development Generalized lack of mesenchymal tissue www.indiandentalacademy.com
  40. 40. Pathogenesis of hemi facial microsomia Early loss of neural crest cells Cells migrating to lateral and lower part of the face (longest path) are most affected. these cells are also important in the formation of great vessels. Cells migrating to central face tend to complete their migratory movement Midline face defects Defect in lower third of the are rare face associated with tetra logy of Fallot www.indiandentalacademy.com
  41. 41. Period of the fetus • This phase extends from 56th day of intrauterine life till birth. • In this period ,accelerated growth of the craniofacial structure occurs resulting in an increase in their size as well as change in proportion between the various structure . www.indiandentalacademy.com
  42. 42. Development of the oral structures • Development of face occurs primarily between 4-8 weeks. • The growth of the cranial ,facial and oral structures begins around the 21 st day after the conception. • At this stage the embryo is about 3mm in size and head begins to take shape. www.indiandentalacademy.com
  43. 43. • there is progressive increase in the size of the embryonic disc, yet the head and tail end of the disc remain relatively close together. • This results in the bulging of the disc upward into the amniotic cavity produces two folds known as head and tail folds. www.indiandentalacademy.com
  44. 44. After the formation of head fold the developing brain and the pericardium form two prominent bulges in the ventral aspect of the embryo. www.indiandentalacademy.com
  45. 45. • In between these ,there is a depression called the stomodeum,the floor of which is formed by the buccopharyngeal membrane which separates the stomodeum from the foregut. www.indiandentalacademy.com
  46. 46. www.indiandentalacademy.com
  47. 47. The buccopharyngeal membrane begins to break down at this stage to allow continuity between pharynx and the stomodeum (primitive oral cavity). www.indiandentalacademy.com
  48. 48. Remnants of the buccopharyngeal membrane are seen between the stomodeum and the pharynx, separating the ectodermally and endodermally covered portions of the first pharyngeal arch. www.indiandentalacademy.com . Human Age: 29 days View: Dorsal
  49. 49. Early in the fourth week of human development the cranial and cervical (neck) regions make up approximately 1/2 of the embryo's length www.indiandentalacademy.com
  50. 50. The branchial arches • Differentiation of the face takes place early in the prenatal life, specifically between the 5-7 weeks after the fertilization. • In the 4th week after the conception, the future face and the neck region located under the forebrain of the future embryo becomes segmented. www.indiandentalacademy.com
  51. 51. • Five branchial arches are formed appearing as rounded, tubular enlargements and are bounded by the clefts and grooves that help in defining each arch. • Mid and lower facial region develop in part, from the first two, named the mandibular and the hyoid arches. www.indiandentalacademy.com
  52. 52. By the time that the anterior neuropore closes, the first and second pharyngeal arches are evident. . Human Age: 27 days www.indiandentalacademy.com View: Lateral
  53. 53. The first, second, third and fourth arches are visible externally. The sixth arch does not form an external elevation. www.indiandentalacademy.com
  54. 54. The maxillary and mandibular prominences of the first arch contribute the upper and lower jaw. The external ear forms from tissues of the first and second arches. The third and fourth arches form very little of the external surface of the neck, their tissues lying deep in the cervical sinus. www.indiandentalacademy.com . Human Age: Sixth week View:
  55. 55. The regions between the pharyngeal arches are termed pharyngeal clefts. The indentation just dorsal to the second pharyngeal cleft is the developing inner ear, the otic pit. www.indiandentalacademy.com Human Age: 27 days View: Lateral
  56. 56. The clefts that separate the pharyngeal arches on the external surface of the embryo are located opposite pharyngeal pouches internally. www.indiandentalacademy.com Human Age: 29 days View: Dorsal
  57. 57. Closing membranes, consisting of ectoderm, opposed to endoderm, separate the pharyngeal clefts from the pouches. www.indiandentalacademy.com Human Age: 29 View: Dorsal days
  58. 58. Each arch contains mesenchyme that is derived in part from neural crest and in part from mesoderm. www.indiandentalacademy.com Human Age: 29 days View: Dorsal
  59. 59. The pharyngeal arches are organized around blood vessels that extend dorsally from the developing heart. www.indiandentalacademy.com
  60. 60. illustrates the relationship of the developing heart and aortic sac to the pharyngeal arches. The arches surround the pharynx and contain aortic arch blood vessels. www.indiandentalacademy.com Human Age: 27 days View:
  61. 61. Nerve supply www.indiandentalacademy.com
  62. 62. The first pharyngeal arch has both a maxillary and a mandibular prominence. Dorsal to the first arch is an elevation formed by the underlying trigeminal ganglion, the sensory ganglion for the nerve that supplies tissues derived from the first arch. www.indiandentalacademy.com Human Age: 29 days View: Lateral
  63. 63. Each of the pharyngeal arches is supplied by a specific cranial nerve. The cells that contribute to the sensory ganglia are derived from neural crest cells and from epibranchial placodes. www.indiandentalacademy.com
  64. 64. Epibranchial placodes are specialized regions of surface ectoderm, the cells of which invaginate to contribute to the formation of the sensory ganglia of cranial nerves V, VII, IX, and X. www.indiandentalacademy.com Human Age: 29 days View: Lateral
  65. 65. Derivatives of the pouches and clefts www.indiandentalacademy.com
  66. 66. www.indiandentalacademy.com
  67. 67. Some of the neural crest cells in each of the arches become cartilage. www.indiandentalacademy.com
  68. 68. www.indiandentalacademy.com
  69. 69. Development of the face www.indiandentalacademy.com
  70. 70. • The developing face is initially represented by the frontonasal region, and the first pharyngeal (branchial, visceral) arch. www.indiandentalacademy.com
  71. 71. • The human face is first characterized by an invagination or the dimple in the surface ectoderm layer appearing just below the forebrain. • As this pit deepens, it forms the outline of the oral cavity and the tissue mass immediately surrounding this oral pit will form the future face. • In the 4th week the posterior boundary of the oral pit comes into contact with the developing foregut. www.indiandentalacademy.com
  72. 72. • As the oral ectodermal plate meet the endodermal lining of the gut, the membrane disintegrate and the continuity between the oral cavity and the gastrointestinal tract is first gained. • At 5th week face appear crowded between the rapidly growing forebrain and the heart which occupy most of the chest cavity at this stage. www.indiandentalacademy.com
  73. 73. Soon the mesoderm covering the developing brain proliferates and forms a downward projection that overlaps the upper part of the stomodeum and this downward projection is called frontonasal process www.indiandentalacademy.com
  74. 74. In the inferior and lateral portion of the frontonasal process, bilateral localize area of the surface ectoderm thickens to form nasal placode www.indiandentalacademy.com
  75. 75. • The growth of the heart affects the development of the face, not only because of the importance of the blood supply to its development but because the face during its early period of rapid growth and organization is crowded between the enlarging forebrain and the pulsating heart. www.indiandentalacademy.com
  76. 76. • Due to migration and proliferation of neural crest cells into the pharyngeal arch the paired structures develop surrounding the stomodeum known as maxillary process and mandibular process • One of the first events in the formation of facial structures is fusion of medial ends of the mandibular process in the midline to form the chin and the lower lip. www.indiandentalacademy.com
  77. 77. • Medial and lateral nasal process are formed due to proliferation of mesenchyme along the periphery of nasal placode. • The center of nasal placode becomes thinner due to loss of ectoderm and leads to formation of nasal pits which are the precursors of the nostrils and the nasal cavities. www.indiandentalacademy.com
  78. 78. • Before the fusion of the medial and lateral nasal process the nasal pit undergoes further elongation. • The raised anterior borders of the nasal pit form the horse shoe shaped structures with the open side below. • As they grow forward, the inferior ends of the horseshoes come into contact with each other. www.indiandentalacademy.com
  79. 79. • The distance between these two pits remains constant during these period however pit themselves increase in height and length. • Since the tissue underlying the each nostril represents the first separation of the nasal cavity from the oral cavity, it has been regarded as the primary palate. www.indiandentalacademy.com
  80. 80. • Due to proliferation of underlying mesenchyme in the max.prominences it moves medially toward each other and toward the medial nasal process. • The medial nasal process of both side also fuse with each other and form intermaxillary segment. www.indiandentalacademy.com
  81. 81. • This segment is important as it gives rise to the philtrum, four incisor teeth, alveolar bone and gingiva surrounding them and primary palate. • A no of facial prominences fuse between 7 to 10 weeks and give rise to a no. of structures. www.indiandentalacademy.com
  82. 82. www.indiandentalacademy.com
  83. 83. • The fusion between the medial nasal process and the maxillary process is a multi step procedure. www.indiandentalacademy.com
  84. 84. •Initially there is contact between the epithelium covering medial border of max. process and the lateral border of the medial nasal process .and form a lamina— known as nasal fin. www.indiandentalacademy.com
  85. 85. • Upon contact adhesion of two epithelial sheets occur and they become fused into a single sheet. • Then degeneration of the sheets occurs, resulting in connective tissue penetration through it. and finally formation of upper lip takes place. www.indiandentalacademy.com
  86. 86. • At the posterior limit of the epithelial fin, the epithelial sheets split apart and produces an opening between the nasal pits and roof of the nasal cavity. • These posterior openings are future internal nares and is the posterior limit of the primary palate. www.indiandentalacademy.com
  87. 87. The medial nasal prominences merge in the midline to smooth the median furrow. www.indiandentalacademy.com
  88. 88. • Later the nasal cavity enlarges posteriorly to form a space overlying the entire oral cavity. • the oral and nasal cavity are separated by the secondary palatal shelves which are termed “secondary palate” as they are secondary to the primary palate. www.indiandentalacademy.com
  89. 89. Development of tongue www.indiandentalacademy.com
  90. 90. Development of the tongue • The development of the tongue is of considerable interest because of its importance in functional matrix, its role in epigenetic and environmental influences on the osseous skeleton as well as its role in dental malocclusion. • Can be studied under following headings • Epithelium • Connective tissue • Muscles www.indiandentalacademy.com
  91. 91. • The tongue arise in the ventral wall of the primitive oropharynx from the inner lining of the first four pharyngeal arches www.indiandentalacademy.com
  92. 92. • During the 4th week of i.u life paired lateral thickenings of mesenchyme appear on the internal aspect of the first pharyngeal arch to form lingual swellings, a centrally located swelling also develops known as Tuberculum impar www.indiandentalacademy.com
  93. 93. • The lingual swelling grow and fuse to form the mucosa of anterior 2/3 of the tongue • Posterior 1/3 develops from hypo pharyngeal eminence derived from 3 and 4th arch. www.indiandentalacademy.com
  94. 94. • Around the 5th week of i.u life, the ventral aspect of the 2nd 3rd and 4th pharyngeal arches elevate into an united single prominence known as copula which degenerate without significant contribution www.indiandentalacademy.com
  95. 95. www.indiandentalacademy.com
  96. 96. • Around the fused lingual swellings there is epithelial proliferation into the underlying mesenchyme takes place. Degeneration of the central cells of this horse shoe shaped lamina forms a sulcus, the liguogingival groove, which frees the body of he tongue from the floor of the mouth except for the midline frenulum of the tongue. www.indiandentalacademy.com
  97. 97. www.indiandentalacademy.com
  98. 98. The junction of the anterior twothirds and posterior third of the tongue is at the terminal sulcus. The foramen cecum is the site at which the thyroid gland forms and invaginates. www.indiandentalacademy.com
  99. 99. Development of connective tissue and muscle • Connective tissue develop from local mesenchyme • Tongue muscle develop from the occipital myotomes and are supplied by hypoglossal nerve • Taste buds arise by inductive interaction between epithelial cells and invading gustatory nerve cells from the chorda tympani, glossopharyngeal and the vagus nerve. the fungiform papillae are first to be develop at 11 weeks i.u. the circumvallate papillae develop at 2 -5 months i.u. www.indiandentalacademy.com
  100. 100. Development of palate • The palate begins to develop early in the six week and the process is completed in 12 week. • The entire palate develops from 2 structure –the primary palate and the secondary palate. • The primary palate is the triangular shaped part of the palate anterior to the incisive foramen which arises from the fusion of two medial nasal prominences. www.indiandentalacademy.com
  101. 101. The medial nasal prominences contribute the tissues that will form the anterior part of the palate, the primary palate (circled). . www.indiandentalacademy.com
  102. 102. • The secondary palate arises from the paired lateral palatine shelves of the maxilla which are oriented in a superior –inferior plane with the tongue interposed www.indiandentalacademy.com
  103. 103. A frontal cut illustrates that the tongue is initially interposed between the secondary palatal shelves. www.indiandentalacademy.com
  104. 104. • Later the lateral palatine shelves of the maxilla become elongated and the tongue becomes relatively smaller and moves inferiorly. www.indiandentalacademy.com
  105. 105. • This allows the shelves to become oriented horizontally to approach one another and to fuse in the midline www.indiandentalacademy.com
  106. 106. • The median palatine raphe is the clinical remnant of fusion between palatine shelves. • The lateral palatine process also fuses with the nasal septum and the primary palate. • The fusion between the palatine shelves and the nasal septum proceeds in an antero-posterior direction beginning in the ninth week. www.indiandentalacademy.com
  107. 107. www.indiandentalacademy.com
  108. 108. Fusion of the palatal shelves with each other and with the nasal septum separates the nasal cavities from the oval cavity. www.indiandentalacademy.com
  109. 109. www.indiandentalacademy.com
  110. 110. Pathogenesis of cleft lip and cleft palate • This occurs when mesenchymal connective tissue from different embryological structure fail to meet and merge with each other. • The common form of cleft lip is a result of failure of fusion of the median nasal process with the max process. • It may be unilateral or bilateral and may extends into the alveolar process. www.indiandentalacademy.com
  111. 111. • Cleft palate is the result of failure of the lateral palatine process to fuse with each other ,with the nasal septum or with the primary palate. www.indiandentalacademy.com
  112. 112. www.indiandentalacademy.com
  113. 113. www.indiandentalacademy.com
  114. 114. Further growth of the face:-• Even at this early stage the growth pattern of the face is downward and forward as it grows out from between these two organs. • Important related occurrences are the flexures that occur during the 4 th week in the region of the future neck. • The brain flexes ventrally, then dorsally and as a result the head becomes more erect. www.indiandentalacademy.com
  115. 115. Development of the skull • The skull is formed by mesenchymal connective tissue around the developing brain. www.indiandentalacademy.com
  116. 116. • The development of the skull is considered in two componentsNeurocraniumcalvaria and base of the skull and derived from occipital somites. Viscerocraniumskeleton of face and other associated structures Derived from neural crest ectoderm. Each component has some structure that form by endochondral ossification (cartilaginous component) and other structures that form by intramembranous ossification (membranous component) . www.indiandentalacademy.com
  117. 117. Cartilaginous neurocranium • Consists of several cartilages that fuse and undergo endochondral ossification to give rise to base of the skull. • The cartilaginous junction between two bones are called synchondroses. • The new cartilage cells continually form in the center of the synchondroses,move peripherally and then undergo endochondral ossification along the lateral margins. www.indiandentalacademy.com
  118. 118. The bone formed by this process are • • • • • Occipital bone Body of the sphenoid bone Ethmoid bone Vomer Petrous and mastoid part of the temporal bone. www.indiandentalacademy.com
  119. 119. Membranous neurocranium • These arises by the intramembranous ossification of the mesenchyme around the developing brain. • Sutures (syndesmoses) are uncalcified dense sheets of connective tissue that separate the bones of the calvaria. • These sutures are also derived from two sources-neural crest cells (sagittal suture) and paraxial mesoderm (coronal suture). • When sutures come together they form a region of dense connective tissue known as FONTANELLES. • They help the calvaria to change the shape during birth by a process called MOLDING. www.indiandentalacademy.com
  120. 120. The bones formed by this process are • Flat bones of calvaria. • Superior portion of the frontal ,occipital and parietal bones. www.indiandentalacademy.com
  121. 121. viscerocranium • Includes the facial skeleton arises from the pharyngeal arches. Cartilaginous component -includes middle ear ossicles,the styloid process of temporal bone,the hyoid bone and the laryngeal cartlilages. Membranous viscerocranium —includes maxilla ,zygomatic bone, the squamous temporal bone and the mandible. except for the mand condyle,and the midline of the chin. www.indiandentalacademy.com
  122. 122. Development of mandible and TMJ • The template for the mandible is laid down by meckle’s cartilage of the first pharyngeal arch. • Initial intramembranous ossification occurs at 6 week post conception, the earliest of bones to ossify. • The primary ossification center is located at the side of bifurcation of the inferior alveolar nerve into the incisive and the mental nerve. • Then it spreads anteroposteriorly on the lateral aspect of the meckle’s cartilage to encompass the cartilage which later disintegrates. www.indiandentalacademy.com
  123. 123. www.indiandentalacademy.com
  124. 124. • Secondary cartilage develops at the site of coronoid and condylar process and at the angle. • By 11 weeks secondary cartilage has developed, forming the condylar head which is separated from the temporal bone by a fibrous connective tissue. and commencement of ossification of this cartilage takes place at 18-19 weeks. • The cartilaginous head of the condyle enveloped in the fibrous covering that is continuous with the joint capsule, persists and function as a growth center until about the 25 year of post natal life. • Each half of the mandible develops as a single skeletal system in which meckle's cartilage serves as an initial template but does not contribute directly to the formation of mandible. www.indiandentalacademy.com
  125. 125. 9 weeks 16 weeks 24 weeks www.indiandentalacademy.com 30 weeks
  126. 126. • As the two halves of the mandible continue to grow fibrous connective tissue known as symphyseal cartilage unite the two halves of the mandible and serve as a growth site until the first year after birth by which time it is calcified. • The angle of the mandible at birth is about 130 degree with the condyle,thus nearly in the line with the body. • Later all these cartilages, together with the ventral most tip of the meckle’s cartilage, ossify endochondrally to conjoin with the membranous bone of the body of the mandible. www.indiandentalacademy.com
  127. 127. • Forward growth Backward growth height Deposition of new bone along the anterior surface of the mandible Accretion along the post. border of the ramus extending from condyle to the angle of the mandible. Development of the dentition and the alv.bone. www.indiandentalacademy.com
  128. 128. www.indiandentalacademy.com
  129. 129. Development of maxilla • A primary intramembranous ossification center appear for each maxilla in the 8 th week IU at the termination of infraorbital nerve just above the canine tooth dental lamina. • two further itramembranous premaxillary centers appear anteriorly on each side in the 8th week and rapidly fuse with the primary maxillary center. www.indiandentalacademy.com
  130. 130. Prenatal changing relationship between maxilla and mandible • During intra uterine development, the relative size of the maxilla and the mandible vary widely. • Initially the mandible is considerably larger than the maxilla, a predominance later diminished by the relatively greater development of the maxilla, changing the jaw relationship from angle class III to class II. www.indiandentalacademy.com
  131. 131. • At about 8 weeks post conception, the maxilla overlaps the mandible. subsequently the mandible grows more rapidly, equaling the maxilla by 11 weeks post conception. • Mandibular growth then lags between the 13 th to 20th weeks, due to a change over from MECKLE’S cartilage to the condylar secondary cartilage as the main growth center of the mandible. • At birth the mandible is generally retrognathic to the maxilla ,although the two may be of equal size. www.indiandentalacademy.com
  132. 132. Clinical significance •Fibroblast growth factor (FGFs) and fibroblast growth factor receptors (FGFRs) play a important role in the skeletal dysplasia by controlling the cellular events such as proliferation ,differentiation, and migration. •FGFR-1 and FGFR-2 are expressed in prebone and precartilage regions including craniofacial structure. •FGFR-3 is expressed in cartilage growth plates of long bones. www.indiandentalacademy.com
  133. 133. FGFR-1 FGFR-2 FGFR-3 Osteogenic differentiation + + proliferation Unclear role www.indiandentalacademy.com mutation craniosynos tosis dwarfism
  134. 134. • Crnioschisis (anencephaly) crniosynostosis www.indiandentalacademy.com acrocephaly scaphocephaly plagiocephaly
  135. 135. The fetal period—3—9 month • Craniofacial changes—by the 3rd month face assumes more human appearance. • During the fetal period the head increases in length from approx. 12 to 74mm and height from 20 to 100mm thus maintaining a fairly constant ratio of width to length but not to the height. • Prior to 5th month the height increase is greatest where as length and width increases are proportional. www.indiandentalacademy.com
  136. 136. • At birth the cranial vault is approx.8times larger than the face. • In the embryonic period the cranium to face ratio may be as high as 40:1 dropping at 4 months to 5:1 because of the differentially more rapid facial growth during this period. • The cranium then grows faster in the late prenatal months to attain 8:1 ratio at birth. which again changes to 2:1 in adults due to post natal facial growth. • At the same time the no of skeletal bones is reduced from 45 separate bones at birth to 22 in adult. www.indiandentalacademy.com
  137. 137. Development of teeth • By the 7th week, the epithelial labial lamina develops on the perimeter of the max. and the mand. process . • This wedge of epithelial cells penetrates the underlying connective tissue to separate the tissue of future alveolar ridge from the lip. • At the same time a second lamina lingual to the labial lamina appears and grows into the alveolar ridge.—known as dental lamina which at regular intervals will give rise to enamel organ which will ultimately develop into tooth. www.indiandentalacademy.com
  138. 138. www.indiandentalacademy.com
  139. 139. Molecular regulation of tooth development • Tooth development represents a classic example of epithelium and neural crest derived mesenchymal interaction. • Bud stage---regulation center —bud epithelium • Cap and bell stage (enamel knot)-- regulation center –mesenchyme • BMPs,FGFs ,sonichedgehog,MSX1and 2 interact in complex pathway to produce cell differentiation and patterning for each tooth. www.indiandentalacademy.com
  140. 140. Development of the salivary gland • All three major glands develop during 6—8 weeks due to proliferation of the oral mucosa epithelium into the underlying mesenchyme. • The connective tissue around the developing glands forms the capsule as well as grow into the glands to subdivide them into the lobules. • The acini of the mucous gland become functional during the 6th week where as serous gland become functional by birth, www.indiandentalacademy.com
  141. 141. conclusion • The clinician’s requirement of the anticipated endpoint of growth and development of the face to determine whether orthosurgical intervention is desirable is one of the great challenges with which developmental biologists are confronted. • The hope of biomimetic intervention by genetic engineering and molecular factors signaling utilization in controlling growth, once considered only a remote possibility is now becoming ever more realistic. • With the increasing identification of growth factors ,genes, and chromosomes responsible for the development of the face orthodontists are now in a better position to advise patterns of the ultimate outcome of prognosis of various dentofacial malformation and malocclusions of their progeny. www.indiandentalacademy.com
  142. 142. References:--• Geoffry H.Sperber—New insights in facial development—Seminar in orthodontics,March 2006,vol-12,no-1,page,4-10. • Vinod Krishnan----Neural crest cells,homeobox genes and craniofacial development----J Ind Orthod Soc 2002,35,page no.42—50. • Cobourne M.T---Construction for the modern head—current concepts in craniofacial development—J of Orthod,2000,vol27,page,307-314. www.indiandentalacademy.com
  143. 143. • Vinod Krishnan---Genomics and orofacial clefts-J Ind Orthod Soc 2003,vol--36,page no.39—51. • Graham A ,Okabe M et al—the role of the endoderm in the development and evolution of the pharyngeal arches— Journal of Anatomy2005,vol-207,page,479-487. • Helms JA, Cordero D et al—New insights into craniofacial morphogenesis— Development,2005,vol-132,page,851-861. www.indiandentalacademy.com
  144. 144. • Tapadia MD,Cordero DR et al—It’s all in your head;new insights into craniofacial development and deformation-- Journal of Anatomy-2005,vol207,page,461-477. • Radlanski RJ et al—Bone remodelling of the human mandible during prenatal development— J Orofacial Orthop ,2001,vol-62, page ,191-201. • Trenouth MJ—Changes in the jaw relationships during human foetal cranio-facial growth-Br J Orthod 1985,vol-12, page,33-39. www.indiandentalacademy.com
  145. 145. • Williams R.Proffit----Contemporary orthodontics —3rd edition.St.Louis,CV Mosby,2005.page.6393. • Sadler TW;-- Langman’s medical embryology— 2004,Williams & Wilkins Co.edition-9.page.363401. • Samara E.Bishara---Textbook of Orthodontics— WB Saunders,2003 • Thesleff I ,Sharpe P— Signaling networks regulating dental development-Mech Dev.1997,vol-67,page 111 www.indiandentalacademy.com
  146. 146. • P.A.Mossey —The heritability of malocclusion.part-1---Genetics principles and terminology—BJO 1999 June,vol.26,page.103— 113. • Kalevi Koski et al—cranial growth centers; facts or fallacies?—Am J Orthod.1968Aug-Page-566583 • Bernard G.Sarnat---growth pattern of the mandible: some reflections-- Am J Orthod.1986,Sep,vol-90.Page-221—233. • Irma Thesleff—Homeobox genes and growth factors in regulation of craniofacial and tooth morphogenesis—Acta Odontol Scand,1995vol.53,page,129-134. www.indiandentalacademy.com
  147. 147. • Jiang X et al-Tissue origins and interactions in the mammalian skull vault—Dev.Biol 2002 ,vol206.page-106-11. • Cavazzana-Calvo M et al—The future of gene therapy,--Nature2004,vol.427,page779-781 • Vanden Boogard et al—MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans—Nature Genet.2000vol.24,page,342—343. • Moore –Persaud ---The developing human:Clinical oriented embryology.—Saunders 2003Philedelphia,page.201—238 www.indiandentalacademy.com
  148. 148. www.indiandentalacademy.com Leader in continuing dental education www.indiandentalacademy.com

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