SECTION                              II                      Growth of Face and                     Craniofacial Complex  ...
Chapter-07.indd 80   9/29/2012 12:31:59 PM
Prenatal development of the                                      foetus with reference to                                 ...
Section II: Growth of face and craniofacial complex                                                                       ...
Chapter 7: Prenatal development of the foetus with reference to craniofacial region                     10 mm             ...
A                                                                              B    Section II: Growth of face and craniof...
A                  Amniotic cavity                                       B         Notochordal plate                      ...
Neurulation                                                            tube is the primordium of the central nervous syste...
A                                       Dorsal end             B                                                          ...
Section II: Growth of face and craniofacial complex                                                              Epidermis...
arch. Crest cells from rhombomere 4 populate the 2nd arch,                                                                ...
Table 7.5 Derivatives of pharyngeal pouches                       and the upper one-third of the face. Similarly, the rhom...
A                                                                 B                                                       ...
cartilaginous nasal septum. Early in the development, the                  During the initial stages of formation, the epi...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order...
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Sample chapter Orthodontics Diagnosis and Management of Malocclusion and Dentofacial Deformities, 2e by Kharbanda To order call sms at +91 8527622422

  1. 1. SECTION II Growth of Face and Craniofacial Complex Chapter 7 Prenatal development of the foetus with reference to craniofacial region Chapter 8 Concepts of growth and development Chapter 9 Postnatal growth of face and craniofacial region Chapter 10 Altered orofacial functions and development of face and occlusion 79Chapter-07.indd 79 9/29/2012 12:31:58 PM
  2. 2. Chapter-07.indd 80 9/29/2012 12:31:59 PM
  3. 3. Prenatal development of the foetus with reference to craniofacial region Neeraj Wadhawan, Ram S Nanda, OP Kharbanda 7 Chapter Outline ◗ Introduction ➧ Formation of eyes ◗ Pre-implantation period ➧ Formation of ears ◗ Pre-somite period ➧ Formation of nasal cavity ◗ Somite period ➧ Formation of nasolacrimal duct ➧ Neurulation ➧ Development of palate ➧ Development of the neural crest ➧ Development of tongue ➧ Development of the skeleton ◗ Genetic regulation of craniofacial development ➧ Pharyngeal apparatus ◗ Clinical implications ➧ Pharyngeal arches ➧ Craniofacial syndromes due to defective ◗ Post-somite period genetic control ◗ Foetal stage ➧ Branchial arch syndromes ◗ Development of craniofacial structures ➧ Synostosis syndromes ➧ Development of face ◗ Summary 81 Introduction 2. Somite phase. Lasts from 21st to 31st day; approximately 4th week and early 5th week; characterised by the for- mation of the dorsal metameric segments of the body T he human foetus develops from the fertilisation of an oocyte by a sperm to form zygote. The event usually (neural tube, somites, etc.), establishment of the basic occurs while the oocyte is still in the fallopian tube body plan, polarity and patterns of the major organ (Fig. 7.1). Following fertilisation, a series of important systems. changes occur in the zygote giving rise to an embryo. The 3. Post-somite phase. Lasts from 32nd to 56th day; late sequence of events can be summarised as shown in Figure 7.2. 5th–8th week; characterised by the development of the Broadly speaking, the intrauterine period can be divided external body features and the further development into:1,2 and differentiation of the basic structure.2 1. Pre-implantation period. The first 7 days following fertili- Weeks 4 through 8 are especially important because major- sation. ity of tissues and organ systems differentiate during the period from the original three germ layers (Table 7.1).1–3 2. Embryonic period. From 7th day to 8th week after fertili- The embryonic period can also be divided, on the basis of sation. morphogenetic development of the embryo, into 23 stages 3. Foetal period. Ninth week to term—characterised by starting from fertilisation (Fig. 7.3). These are popularly growth and expansion of the already established body known as Carnegie stages,4 named after Carnegie Institute of structures with little differentiation or new organ for- Washington, USA, and are based on the work of Streeter mation. A highlight of the foetal period is the establish- (1942)5 and O’Rahilly and Müller (1987).6 ment of the ossification centres and the starting of the foetal movements.1 The embryonic phase can be further divided into:1–3 Pre-implantation period1−3 1. Pre-somite phase. Encompasses the 2nd and 3rd weeks after fertilisation; characterised by the differentiation of During the first 2–3 days, the single celled zygote, 140 μm in the three germ layers and the formation of the embryonic size, divides progressively to form a 16-celled cluster called adnexa (foetal membranes) from the inner cell mass. morula. With further cell division, the morula forms aChapter-07.indd 81 9/29/2012 12:31:59 PM
  4. 4. Section II: Growth of face and craniofacial complex Zygote 2 cells stage (30 hours) Morula (day 3) Blastocyst (day 4–5) Blastocele Trophectoderm or trophoblast Ampulla Endometrium Uterine wall Implantation Syncytiotrophoblast (day 6) Fertilisation (day 0) Secondary oocyte at metaphase Figure 7.1 Initial stages of embryonic development from the time of fertilisation to implantation in the uterine mucosa. It is the blastocyst stage at which implantation occurs within the uterine wall approximately 6 days after fertilisation 100-celled structure called blastocyst, which implants in the uterus at around 7th day post-conception. Within the blastocyst a fluid-filled cavity develops which divides the cells into the outer sphere of cells and an inner cell mass. First 3 months 3–6 6–9 months The outer sphere of cells forms trophoblast while the inner cell mass forms the embryo. The trophoblast is responsible Figure 7.2 Stages of foetal development. Most significant events of for the development of the chorionic villi and thus, is impor- life occur during the first trimester and it is hence designated for a tant for the nutrition of the developing embryo. larger distance than the 2nd and 3rd trimesters 82 Table 7.1 Chronological sequence of events during the embryonic period Time from conception Significant events in craniofacial region 14 days Primitive streak appears; formation of oropharyngeal membrane 17 days Neural plate formation commences 20 days Appearance of neural folds; formation of neural crest. Otic placodes appear 21 days Neural folds fuse; migration of neural crest cells starts 24 days Frontonasal process and mandibular arch appear; optic vesicles and olfactory placodes appear 26 days 2nd arch forms; maxillary process starts to differentiate; adenohypophyseal pouch appears 28 days 3rd and 4th arches develop; dental lamina appears; oropharyngeal membrane disintegrates 32 days Lateral nasal process appears; otic and lens vesicles form 33 days Medial nasal process develops; nasal pits form, are wide apart and face laterally 37 days Nasal pits face ventrally; formation of upper lip starts; nasolacrimal groove appears 41 days Medial nasal and maxillary processes fusion starts; nasal cavity separates from oral cavity; upper lip continuity established 44 days Primary palate formation ensues; nose tip forms; eyelids start to form; nasal pits migrate medially; nasal septum forms 47–48 days Nasal fin disintegrates (failure to disintegrate predisposes to cleft lip); rima oris reduces in width; mandible ossification starts 50–51 days Lidless eyes and nasal pits move medially 54 days Eyelids develop; nostrils take final position; auricle of ear develops 56–57 days Eyelid closure commences; eyes still wide apart; face assumes human appearance; head elevated off the thorax; mouth opens; palatal shelves elevate; maxillary ossification starts 60 days Palatal shelves fuse; tooth buds form Source: Adapted from Sperber GH, Sperber SM, Guttmann GD. Craniofacial Embryogenetics and Development, 2nd ed. Peoples Medical Publishing House, USA, 2010, p. 21Chapter-07.indd 82 9/29/2012 12:31:59 PM
  5. 5. Chapter 7: Prenatal development of the foetus with reference to craniofacial region 10 mm 13 (28 days) 14 (32 days) 15 (33 days) 16 (37 days) 17 (41 days) 18 (44 days) Carnegie stages (approximate post-ovulatory days) 19 (47 days) 20 (50 days) 21 (52 days) 22 (54 days) 23 (56 days) Figure 7.3 Selected Carnegie stages of human embryonic development from 28th to 56th day. Carnegie stages divide the human embryonic period into 23 stages from the time of fertilisation to beginning of the foetal period on the basis of important embryonic events Pre-somite period (14–21 days)1−3 Early in the 3rd week, the epiblast proliferates and differ- entiates to give rise to the third layer of cells called the meso- During the second week, two important events occur: (i) the derm through a process called gastrulation, thus establishing trophoblast layer starts to differentiate into bilaminar struc- the trilaminar structure of the embryo. The proliferation of 83 ture which contributes to the formation of the chrionic villi, the epiblast starts at the caudal end of the embryo leading (ii) the inner cell mass divides to form a bilaminar structure to formation of a caudocranial groove starting at the caudal (Fig. 7.4A–D). The bilaminar structure is made of the epi- end. This groove is called the primitive streak. The cranial blast (ectoderm), which consists of columnar cells and forms limit of the primitive streak is marked by the primitive node. the floor of the amniotic cavity, and the hypoblast (endo- From the primitive streak, rapid proliferation of cells leads to derm), which consists of squamous or cuboidal cells form- the formation of the intraembryonic mesoderm which pro- ing the roof of the yolk sac. Meanwhile, the coelomic cavity liferates in all directions between the ectoderm and the develops in the extraembryonic mesoderm (loose tissue endoderm. By the end of the 3rd week, the mesoderm layer adjacent to the embryo) which enlarges progressively to sur- is well established and separates the ectoderm and endo- round the embryo completely except at the stalk where the derm throughout the embryo except two places: the cloacal trophoblastic cells form the chorionic plate. This is the site membrane in the caudal region and the pre-chordal plate at where later the chorion would develop. By the end of the the cranial midline area, where the endoderm and ectoderm 2nd week, the axis of the embryo starts to develop with are tightly adherent. The formation of the three germ layers the appearance of the node at the rostral end (Fig. 7.5A, B). is a critical landmark during the early development of the The node develops under the signalling influence of the embryo. The pre-chordal plate is the future region of the genes Nodal, Hedgehog, FGF (fibroblast growth factor), Wnt, buccopharyngeal membrane. From henceforth, the further and BMP (bone morphogenic protein). The activity of the development of the embryo occurs through the growth and node, through the ciliary movement of the cells, contributes differentiation of the three basic germ layers, namely, ecto- to leftward fluid flow which causes development of left–right derm (1st layer), mesoderm (2nd layer) and endoderm (3rd asymmetry in the developing embryo. At the same time, layer) (Fig. 7.6). Neural crest layer, considered by some as localised thickening of the endoderm at the midcephalic region the 4th germ layer, is essentially a derivative of the ectoder- gives rise to the pre-chordal plate under the influence of the mal layer. The various derivatives of the three germ layers Sonic Hedgehog (SHH). This pre-chordal plate has been are summarised in the Table 7.2. shown to have a head-organising or molecular organising Meanwhile, cells of the primitive streak proliferate fur- function producing signals that pattern the forebrain and ther in a cranial direction and contact the pre-chordal plate help in differentiation of the eye fields. Defects of signalling in (Fig. 7.5B). These cells further invaginate the underlying this region are known to cause holoprosencephaly or agene- tissue to form a structure called the notochord. Notochord sis of the corpus callosum. The pre-chordal layer also con- represents the early midline axis of the embryo helping to tributes the endodermal layer to the oropharyngeal establish the axial skeleton. It also induces the formation of membrane (a membrane which separates the oronasal cav- the neural plate in the overlying ectoderm which later gives ity from the pharyngeal cavity during early development). rise to the neural ectoderm.Chapter-07.indd 83 9/29/2012 12:32:13 PM
  6. 6. A B Section II: Growth of face and craniofacial complex Endometrial Blood vessels stroma Syncytiotrophoblast Epiblast Cytotrophoblast Hypoblast Exocoelomic (Heuser’s) membrane Endometrial Exocoelomic cavity epithelium Epiblast Hypoblast Blastocyst cavity Amniotic cavity D C Trophoblastic lacunae Syncytiotrophoblast Extraembryonic mesoderm Connecting Amniotic cavity stalk Hypoblast Bilaminar embryonic Exocoelomic cavity disc (primitive yolk sac) Secondary yolk sac Exocoelomic membrane Extraembryonic coelom Cytotrophoblast (chorionic cavity) Exocoelomic cyst Figure 7.4 Early stages of development of the human embryo. A. Seven-day-old human blastocyst showing the trophoblastic and amniotic layers. A small amniotic cavity is developing. B. Nine-day-old human blastocyst. The hypoblast layer extends to enclose a cavity called 84 exocoelomic cavity (primary yolk sac). C. Twelve-day-old blastocyst. The exocoelomic cavity and the amniotic cavity increase in size. The extraembryonic mesoderm fills the gap between the cytotrophoblast layer and the exocoelomic cavity. D. Thirteen-day-old blastocyst. Formation of extraembryonic coelom occurs by the breakdown and coalescence of the fluid filled spaces in the extraembryonic mesoderm. Cells from the hypoblast migrate to displace the exocoelomic cavity away from the embryo proper and encase a new space called the secondary yolk sac. The exocoelomic cavity is reduced into a remnant called the exocoelomic cyst A B Pre-chordal plate Pre-chordal plate Cut edge of amnion Cut edge of amnion Pre-notochordal Primitive cells (Hensen’s) node Primitive node Primitive streak Primitive streak Cloacal membrane Figure 7.5 A. Cut section through the amniotic cavity of a third week embryo showing the dorsal surface of the embryo proper. The formation of the primitive node and the primitive streak defines the axis and the poles of the embryo. B. Dorsal migration of the surface epiblast cells along the primitive streak towards the rostral end of the embryo (arrows). Subsequently, cells derived from the epiblast also invaginate between the epiblast and the hypoblast laterally to form the intraembryonic mesoderm (lines) Somite period (21–31 days)1−3 of the developing central nervous system on the dorsal The somite period is characterised by establishment of the aspect leads to the folding of the embryo over its ventral primordia of most of the important organ systems like the aspect thus forming a C-shaped structure at around 4 weeks gut, kidneys, adrenals, heart, lungs and others. Between (Fig. 7.7A, B). The folding leads to incorporation of the sec- the 21st and 31st days the embryo changes its form from a ondary yolk sac into the embryonic structure. The secondary flat disc to a tubular structure. Simultaneously, rapid growth yolk sac contributes to the formation of the gut.Chapter-07.indd 84 9/29/2012 12:32:24 PM
  7. 7. A Amniotic cavity B Notochordal plate Chapter 7: Prenatal development of the foetus with reference to craniofacial region Primitive pit Ectoderm Mesoderm Epiblast (intraembryonic) Cloacal membrane Prochordal plate Wall of yolk sac Yolk sac Endoderm Developing notochord Epiblast Primitive node Primitive streak C D Notochordal plate Amnioblasts Ectoderm Mesoderm (intraembryonic) Endoderm Hypoblast Newly forming mesodermal cells Figure 7.6 Sections through developing embryo in the third week. A. Mid-sagittal section of embryo shows the development of the embryonal axis and the primitive notochord. B, C. Transverse section shows the formation of the third germ layer and the developing notochord. D. Transverse section through the cranial end of the primitive streak in a third week embryo showing gastrulation (at the plane marked in Fig. 7.6A). Cells from the epiblast layer differentiate and migrate extensively between the epiblast and the hypoblast to form the intraembryonic mesoderm (the third germ layer) 85 Table 7.2 Derivatives of the three germ layers Layer Derivatives Ectoderm Surface ectoderm Epidermis, hair, nails, glands of skin, tooth enamel, mammary glands, adenohypophysis, placodal derivatives (inner ear, lens) Neural tube ectoderm CNS (brain and spinal cord), retina, neurohypophysis, pineal body Neural crest Neurons and glia of peripheral nervous system (sensory, sympathetic, parasympathetic systems), Schwann cells, chromaffin cells of adrenal medulla, melanocytes, pharyngeal arch cartilage, most of facial skeleton and facial connective tissue (from ectomesenchyme), dentin and cementum, middle ear bones Mesoderm (head) Pre-chordal plate Several eye muscles Paraxial mesoderm Several eye muscles, skull bones, head muscles, some connective tissue Cardiogenic mesoderm Heart Mesoderm (trunk) Notochord Inter-vertebral discs (nuclei pulposi) Paraxial Most of the body skeleton, muscles of trunk and limbs, dorsal dermis and connective tissue Intermediate mesoderm Kidneys, ureters, somatic gonad, adrenal cortex, blood and blood vessels Lateral plate (somatic and Connective tissue and muscles of viscera, serosa, primitive heart, blood and lymph cells, smooth splanchnic) muscle, spleen, and adrenal cortex Endoderm Endoderm Epithelial lining of respiratory tract, lungs, gut, bladder, part of urethra; parenchymal cells of tonsils, thymus, thyroid, parathyroid, liver, pancreas; epithelial lining of tympanic cavity and auditory tube Source: Adapted from; Finkelstein MW. Overview of general embryology and head and neck development. In: Textbook of Orthodontics, Bishara SE (ed.), Philadelphia, Saunders, 2001Chapter-07.indd 85 9/29/2012 12:33:48 PM
  8. 8. Neurulation tube is the primordium of the central nervous system and its Section II: Growth of face and craniofacial complex anterior end enlarges to form the three segments of the Neurulation is the process of development of the neural brain, forebrain, midbrain and hindbrain. Around the same plate, neuroectoderm and the neural tube. During the 3rd time, the lens and otic placodes begin to form as outgrowths week of development the notochord induces the overlying from ectoderm at the cranial end of the embryo. These later ectoderm to thicken and differentiate into the neural plate. give rise to the eye and the inner ear respectively. Experiments have shown that chordamesoderm (a median strip of mesodermal cells extending through the length of the embryo) and pre-chordal plate (in the anterior region) also Development of the neural crest play a significant role in inducing neural plate formation. In Neural crest refers to a special collection of cells which addition, the chordamesoderm may be responsible for devel- arise in the crest of the neural folds during the process of oping the organisational plan of the head. The neural plate neurulation (Fig. 7.10). It consists of pleuripotential cells, grows caudally towards the primitive streak (Fig. 7.8). At ectomesenchymal in origin, induced by interaction WNT around the 20th day post conception, the lateral edges of activation and BMP inhibition signal pathways. These cells the neural plate elevate to form the neural folds which are characterised by their tendency to extensively migrate enclose a neural groove in the midline (Fig. 7.9A–D). along the natural cleavage planes between the three germ At the 22nd day post-conception, the neural folds start to layers, usually beginning at about the time of closure of fuse with the counterpart of the other side over the neural neural tube (Fig. 7.11). They divide as they migrate, giving groove. The fusion occurs first in the region of the future rise to cell masses which are much bigger at the destination occipital area (area of 3rd to 5th somites) and proceeds both than at their origin. Once they reach their pre-determined cranially and caudally to produce the neural tube. The neural location they differentiate into specific tissues according to the morphogenetic fields and give rise to many important tissues both in the head and neck (Fig. 7.12) as well as in the trunk region. In the head and neck region, they form the complete mesenchyme of the upper facial region and sur- C round the mesodermal cores of the lower facial region. Cells that migrate ventrally and caudally encounter pharyngeal endoderm that induces the formation of the pharyngeal arches. Those which migrate to the trunk region give rise to neural, endocrine and pigment cells (Table 7.3). 86 Greatest length Development of the skeleton1−3 Following the formation of the neural plate and the noto- chord, the intraembryonic mesoderm differentiates into three R types of cell masses depending upon the: A B 1. Lateral plate mesoderm Figure 7.7 Schematic diagram showing the folding of the embryo over its ventral aspect due to exaggerated growth on the dorsal aspect 2. Intermediate mesoderm *c = caudal; r = rostral 3. Paraxial mesoderm. Rostral end Neural Neural plate Neural plate groove Pre-chordal Pre-chordal plate plate Notochordal process 18th day 19th day Caudal end 20th day Figure 7.8 Schematic diagram of a horizontal section through the dorsal surface shows the growth of the neural plate. The primitive streak shortens only marginally while the embryo and the neural plate continue to grow. This reduces the relative size of the primitive streak (Redrawn from Human Embryology. Larsen WJ, Sherman LS, Potter SS eds. Churchill Livingstone pub. UK, 2001, Fig 2.13)Chapter-07.indd 86 9/29/2012 12:34:00 PM
  9. 9. A Dorsal end B Chapter 7: Prenatal development of the foetus with reference to craniofacial region Neural groove Neural plate Neural crest Neural crest Neural crest Paraxial Ectoderm mesoderm Mesoderm Endoderm C Neural tube Neural crest D Paraxial mesoderm Somite Developing notochord Notochord Lateral plate Endoderm mesoderm Ventral end Figure 7.9 A–D. Transverse section through the developing embryo showing the folding of the neural plate to form the neural tube. (Adapted from Kandel E, Schwartz JH, Jessel TM (eds). Principles of Neuroscience, 4th edn., McGraw-Hill Publication, 2002) The lateral plate mesoderm and the intermediate mesoderm give rise to a variety of tissues and organs throughout the Developing neural crest body, the description of which is beyond the scope of this text. The paraxial mesoderm is of greater concern to dental professionals as it is intimately associated with the develop- ment of the cranial structures. Paraxial mesoderm develops adjacent to the notochord 87 A Neural groove along the dorsal surface of the embryo. On further differen- tiation, its rostral end gives rise to certain elevated masses of tissues in the cranial region called the somitomeres. These somitomeres are situated in the paraxial region of the noto- chord. The caudal paraxial mesoderm gives rise to similar Median hinge point structures in the more caudal part of the embryo which are B called somites. Each somite has three basic parts differing in Neural fold location each of which gives rise to different tissues: 1. Sclerotome: Ventromedial part; gives rise to the verte- Neural crest bral region except in occipital region. 2. Dermatome: Lateral part; gives rise to the dermis of skin. 3. Myotome: Intermediate portion; gives rise to the mus- cles of trunk and limbs and some craniofacial muscles. C Approximately 42–44 paired somites are known in human embryo, of which four are occipital and eight are cervical (somitomeres in the craniofacial region) (Fig. 7.13). Neural crest Pharyngeal apparatus D The pharyngeal apparatus consists of a series of bilaterally paired arches, pouches (clefts), grooves and membranes. The pharyngeal arches are seen as paired tubal elevations on the ventral surface of the embryo on either side of the midline. They are partially separated on the external surface of the embryo by fissures called pharyngeal grooves or clefts while the pharyngeal pouches partially separate the arches Figure 7.10 Schematic diagram of transverse section through the on the internal aspect. The pharyngeal membranes represent dorsal end of embryo showing the formation of the neural crest the tissue interposed between pouches and clefts and connect cells (neurulation) in the lateral aspect of the neural folds adjacent arches.7Chapter-07.indd 87 9/29/2012 12:34:14 PM
  10. 10. Section II: Growth of face and craniofacial complex Epidermis Neutral tube Caudal Dermamyotome Sclerotome Notochord Path 2 cells travel a dorsolateral Aorta route between the epidermis and Post. the dermamyotome Ant. Somite Rostral Path 1 cells travel ventrally through the anterior sclerotome Figure 7.11 Schematic diagram showing neural crest cell migration in the trunk region of chick embryo. Path I cells travel ventrally through the anterior portion of the sclerotome. Path II cells travel along a dorsolateral route below the surface ectoderm (Reproduced with permission from Gilbert SF, Sunderland MA (eds). Developmental Biology, 6th edn., Sinauer Associates, 2000, Fig. 13.2) Pharyngeal arches Developing head Development of the tissues of the neck and the major part 88 of the face is largely dependent on the cranial somitomeric mesoderm. The cells of the somitomeric mesoderm migrate Arrows show path of into the ventral region of the embryo at the rostral end, and migration of cranial with a minor contribution from the lateral plate mesoderm, neural crest cells in to form the future pharyngeal arches. The pharyngeal the head and neck region of the arches arise as outgrowths on the ventral surface of the developing Branchial arches embryo rostral to the foregut in relation to the ventral sur- embryo face of the rhombencephalon during the 4th week of intra- uterine (IU) life. Embryologically, the arches are derived Figure 7.12 Migration of the cranial neural crest cells into the from the cranial neural crest cells which migrate from spe- head and the branchial arches to form structures of face and neck cific segments of the hindbrain (rhombomeres) with minor including bones and cartilages. They also produce pigment cells overlap between segments. and cranial nerves (Adapted from Gilbert SF, Sunderland MA (eds). Neural crest cells from rhombomeres 1 and 2 together Developmental Biology, 6th edn, Sinauer Associates, 2000, Fig. 4.16) with caudal midbrain derived crest cells, populate the first Table 7.3 Major neural crest derivatives Organ system Cranial neural crest Trunk neural crest Nervous system Sensory ganglia of cranial nerves: V, VII, IX, X; satellite Sensory spinal ganglia; satellite cells of these cells of sensory ganglia, parasympathetic ganglia of cranial ganglia; parasympathetic ganglia of trunk region; oligodendroglia region; Schwann cells of peripheral neurons Pigment cells Melanophores, xanthophores, erythrophores, iridophores Melanophores, xanthophores, erythrophores, iridophores Endocrine system Calcitonin producing cells, carotid body (type I cells); Adrenal medulla; neurosecretory cells of parafollicular cells of thyroid heart and lungs Mesodermal cells Cranial vault; nose and orbit skeleton; otic capsule; maxilla, Nil (skeleton) minor part of sphenoid Mesodermal cells Dermis, fat, smooth muscles of skin, ciliary muscles of Nil (connective tissue) eye, cornea, connective tissue of glands of head and neck; odontoblasts, part of prosencephalon and mesencephalon; semilunar valves of heart and connective tissue in aorta Muscles Ciliary, dermal smooth muscles, vascular smooth muscles Nil Source: Adapted from Carlson BM. Foundations of Embryology, 6th ed, Tata McGraw Hill, India, 2007, p. 474Chapter-07.indd 88 9/29/2012 12:34:27 PM
  11. 11. arch. Crest cells from rhombomere 4 populate the 2nd arch, Chapter 7: Prenatal development of the foetus with reference to craniofacial region while rhombomeres 6 and 7 contribute to 3rd, 4th and 6th Buccopharyngeal membrane pharyngeal arches. It should be noted that rhombomeres 3 and 5 are depleted of neural crest production and whatever little cells they produce die by apoptosis under the influence of gene BMP4.8 Each pharyngeal arch has its specific apparatus: a spe- cific cartilage that forms the skeleton of the arch, a nerve that supplies the muscles and mucosa derived from the arch, Notochord and an artery (called the aortic arch) (Fig. 7.14).7,8 All these components are well developed in the 1st and 2nd arches Somites except for the arteries.7,8 Pharyngeal arches play a major role in the formation of face, oral cavity, teeth, nasal cavity, pharynx, larynx and neck (Tables 7.4, 7.5). Post-somite period (32–56 days) The post-somite period is characterised by the growth and morphodifferentiation of the previously established organ Cloacal membrane systems. The head becomes large and predominates over the small body. The somites become less conspicuous on Figure 7.13 Schematic representation of a 29-day-old embryo from the external surface. Face starts to show development of the the dorsal aspect showing the somites eye, ear, and nose, which start to resemble the human form. Pharyngeal pouch Endodermal epithelium Artery 1st pharyngeal arch Nerve Cartilage Pharyngeal cleft 89 2nd arch with nerve, Ectodermal artery and cartilage epithelium 3rd arch Mesenchymal 4th–6th arch tissue in 4th arch Laryngeal orifice Figure 7.14 Cut section through the branchial arches in a developing embryo. Each arch has its own neural, vascular supply and cartilage. The arches are grooved on the external surface by pharyngeal clefts and on the internal surface by pharyngeal pouches. The arches are lined externally by ectoderm and internally by endoderm between which lies each arch’s mesodermal core. The 5th arch disappears during development Table 7.4 Derivatives of pharyngeal arches Arch Cartilage; Derivatives Bone Muscles Nerve 1st Meckel’s cartilage; Maxilla, mandible, Masticatory muscles: Trigeminal (V) Derivatives: malleus, incus temporalis, masseter and the Sphenomandibular pterygoids, tensor palatini, ligament, anterior tensor tympani, anterior belly ligament of malleus of digastric 2nd Reichert’s cartilage: Lesser cornu and Muscles of facial expression, Facial (VII) Derivatives: Stylohyoid body of hyoid stapedius, posterior belly of ligament digastric, stylohyoid 3rd – Greater cornu and Stylopharyngeus Glossopharyngeal (IX) body of hyoid 4th and Thyroid cartilage, – Pharyngeal and laryngeal Recurrent laryngeal n. (Br. of CN X), 6th laryngeal cartilages muscles spinal accessory (XI) via the pharyngeal br. of CN X Source: Modified from Hiatt JL, Gartner LP. Textbook of Head and Neck Anatomy, 3rd ed. Baltimore, Lippincott Williams & Wilkins, 2001 Br. = branch; n. = nerve; CN = cranial nerveChapter-07.indd 89 9/29/2012 12:34:48 PM
  12. 12. Table 7.5 Derivatives of pharyngeal pouches and the upper one-third of the face. Similarly, the rhomben- Section II: Growth of face and craniofacial complex Pouch Derivatives cephalic centre induces the differentiation of the middle and lower third of the face, including the external and middle 1st pouch Tympanic cavity and lining of tympanic drum ears. Mastoid air cells Auditory tube The frontonasal process (FNP) develops under the influ- Anterior two-thirds of tongue ence of the forebrain. The forebrain establishes multiple sig- Foramen caecum nalling centres in the ectoderm that covers the future FNP 2nd pouch Pharyngeal tonsils region under the control of the gene SHH. This signalling Palatine tonsils ensures proper descent of the FNP and its differentiation Posterior one-third of tongue into midline organ structures. By the end of the 4th week, Lingual tonsil the face and the forebrain are made by frontonasal process 3rd pouch Inferior parathyroid (middle and front), maxillary processes (laterally placed) Thymus and mandibular process (caudally placed), hyoid arch and Base of tongue glossopharyngeal arch. 4th pouch Superior parathyroid By the 5th week, nasal placodes appear along the inferior Thymus and lateral portion of the FNP. Further development of the Base of tongue nasal placodes in a medial direction in a horse-shoe manner Epiglottis leads to the formation of medial and lateral nasal processes. 5th pouch Ultimobranchial body The area between the two processes gets progressively Parafollicular cells of thyroid depressed to form the nasal pits. These later invaginate to form the nasal cavities. Later in the 5th week, the continued Source: Adapted from Development of the nervous system. In: medial movement of the maxillary prominences pushes the A Textbook of Neuroanatomy. Patestas MA, Gartner LP (eds.), widely separated nasal prominences more medially into the Blackwell Publishing, USA, 2006, p. 15 position of the future nostrils. The fusion between median nasal and maxillary processes, which occurs between 7 and 8 weeks, contributes to the central part of the nose and the Meanwhile, limb buds start to grow and the first foetal mus- philtrum of the lip. The lateral nasal processes form the cular movement may occur at later end of the stage. outer parts of the nose while the maxillary processes form the bulk of upper lip and cheeks. The maxillary processes also fuse with the respective mandibular processes at 7–8 90 Foetal stage weeks forming the angle of mouth. The foetal period is characterised by the rapid growth of the organ systems previously established. Little differentiation of Formation of eyes new tissue systems is seen and the main emphasis remains The eyes develop from a single median set of cells, the optic in the differential growth of various systems. With the primordium, originating in the neural plate in the ventral growth of the body the head, which occupies approximately anterior region of the diencephalon. Under genetic control half of the body length initially, gets reduced to about one- from Cyclops gene, cells from the lateral parts of the optic fourth at birth. Establishment of primary ossification centres primordium differentiate into bilateral lens placodes while also occurs during this period. the central part is suppressed. The lens placodes initially are located on the lateral sides of the developing face but migrate medially with growth of the cerebral hemispheres during 5th–9th week, after which, little movement is seen. Development of craniofacial Simultaneous invagination of the lens placodes occurs, and structures with the formation of optic vesicles, the eye balls start to take their final shape. Development of face Development of the head depends to a large extent upon Formation of ears the prior development of the brain. As discussed earlier, the The ear has three parts which have different origins. The brain starts to develop at the rostral end of the neural tube external ear develops in the neck region as auricular hill- as a series of three vesicles: prosencephalon (forebrain), ocks surrounding the first pharyngeal groove. The internal mesencephalon (midbrain) and rhombencephalon (hind- ear forms from the otic placodes which develop on the brain; rhombomeres 2–7). lateral aspect of the developing head under the influence of The differentiation of human face takes place between the rhombencephalon. The placode later invaginates into the 4th and 7th weeks of intrauterine life (Fig. 7.15A–F). the underlying tissue to form a vesicle which later differenti- In the 4th week, the future face and neck region becomes ates into the inner ear. The middle ear originates from the segmented and located under the forebrain of the embryo. first pharyngeal pouch. The brain tissue exerts an organising influence on the devel- oping face. The prosencephalic centre, a mass of specialised mesodermal tissue derived from the pre-chordal mesoderm Formation of nasal cavity of the primitive streak, induces the differentiation of the The nose arises from the frontonasal process and its deri- visual apparatus, inner ear part of the auditory apparatus vatives, the median and lateral nasal processes, and theChapter-07.indd 90 9/29/2012 12:35:32 PM
  13. 13. A B Chapter 7: Prenatal development of the foetus with reference to craniofacial region Frontonasal prominence Frontonasal prominence Nasal placode Nasal pit Oral plate Oral plate Maxillary process Mandibular arch Maxillary process Mandibular arch Hyoid arch Hyoid arch C D Nasomedial process Nasolateral process Nasolacrimal groove Maxillary process Mandible Hyomandibular cleft 91 E F Nasolateral process Nasomedial process fusing to form philtrum of lip External ear Ear tubercles around hyomandibular cleft Hyoid bone Laryngeal cartilages Figure 7.15 Schematic view of embryonal face development between 4th and 8th weeks. A. Four-week-old embryo. Note the prominent swellings of the developing mandibular processes of both sides. The mandibular processes have fused in the midline. The maxillary processes are starting to bud from the 1st arch. The frontonasal process is yet to descend in the midline. Primitive nasal placodes and optic vesicles (not visible in the picture) are starting to form. B. Five-week-old embryo. The maxillary processes are established and are migrating towards the midline. The descent of the frontonasal process is evident. The frontonasal process divides to give rise to lateral and median nasal processes which surround the nasal pit of each side. The nasal pits are beginning to deepen and are placed wide laterally. The lens placodes are developing on the lateral aspects of developing face. C. Five-and-a-half week embryo. The hyomandibular cleft divides the mandible from the neck region. The nasal pits start to face ventrally. The nasolacrimal groove starts to form. The upper lip starts to form by fusion of the lateral nasal process with the maxillary process. D. Six-week-old embryo. The primitive eye is well established on the lateral aspects of face. Nasolacrimal groove is forming. The descent of the frontonasal process and the medial movement of the maxillary processes continue. The median nasal process and the maxillary process start to fuse separating the nasal and oral cavities. E. Seven-week-old embryo. The MNP fuses with the maxillary process of respective side to complete the upper lip. The maxillary process also fuses with the mandibular process at the lateral margins to form the rima oris. The eye is well formed but lidless and is moving medially to its future position. The ear tubercles establish around the hyomandibular cleft on the lateral aspect. F. Eight-week-old embryo. Facial structure is well recognisable. Eye closure commences and they continue to migrate medially. The nasal pits also migrate medially. Rima oris reduces significantly in size laterally. The external ears are developingChapter-07.indd 91 9/29/2012 12:35:32 PM
  14. 14. cartilaginous nasal septum. Early in the development, the During the initial stages of formation, the epithelium over Section II: Growth of face and craniofacial complex nasal pits become separated from the oral cavity on the the groove proliferates and invaginates the underlying mes- external surface by the fusion of the median and lateral enchyme as a solid cord of cells. Soon, the epithelia of the nasal processes with the maxillary process (Fig. 7.16A–D). lateral nasal process and the maxillary process grow over The nasal pits invaginate the underlying mesenchyme to the invaginated epithelium and fuse with each other. The form the anterior nares. Posteriorly, the nasal cavity is sepa- invaginated epithelium subsequently breaks down to form rated from the stomodeaum by the oronasal membrane. The the hollow lacrimal duct and the lacrimal sac. The ducts nasal pits continue to deepen, and with the disintegration of become completely patent only after birth. Aberrations in the oronasal membrane around the 7th week, the posterior the formation of the nasolacrimal duct lead to formation of nares (primary choanae) are established. Although the nos- oblique facial clefts. trils become patent early in life, they remain plugged with solid structure of epithelial tissue till late in development. Meanwhile, the mesenchyme of the frontonasal process at the site of the future nasal septum develops thickenings, from which originates the nasal capsule. Mesoethmoid, the medial mesenchymal thickenings, are the precursor of the nasal septal cartilage. The two lateral mesodermal thicken- ings, the ectethmoid, give rise to the paired ethmoidal Nasolacrimal (chonchal) and the nasal alar cartilages. The tissue from the groove mesoethmoid develops downwards in the median plane to meet the palatal shelves in the midline dividing the nasal cavity into two halves while the ectethmoid forms the lateral superior, middle and inferior conchae. Formation of nasolacrimal duct3 1 mm The nasolacrimal ducts are bilateral epithelial lined tubes Medial nasal processes which form at the line of fusion of the lateral nasal process Lateral nasal processes and the maxillary process (Fig. 7.17). The ducts connect the Maxillary prominences nasolacrimal sac to the nasal cavity and function to drain Figure 7.17 The nasolacrimal duct originates as the nasolacrimal the lacrimal secretions from the eye. The duct originates groove around 6 weeks after fertilisation. It extends from the medial 92 from the embryonic nasolacrimal groove which runs from end of the developing eye to the primitive stomodeum and grooves the medial end of the eye to the nasal pits. This groove sepa- between the lateral nasal process and the maxillary process on rates the lateral nasal process from the maxillary process. each side A B Breakdown of oronasal membrane Frontonasal process Nasal pit Primitive palate Oral cavity Nasal Oronasal Developing cavity membrane tongue Developing cribriform plate Olfactory nerve C D and olfactory nerve Secondary Nasal cavity palate Maxilla Primary palate Upper lip Oral cavity Lower lip Mandible Figure 7.16 Development of the nasal cavity. A. The primitive nasal pit is separated from the oral cavity by the oronasal membrane. B. Breakdown of the oronasal membrane leads to free communication between the oral and nasal cavity. C. Deepening of the nasal pits leads to increase in size of nasal cavity. The olfactory bulb also starts to establish. The primary palate starts to form. D. The formation of the palate divides the nasal cavity from the oral cavity. The development of the nasal conchae divides the nasal cavity into superior, middle and inferior meatusChapter-07.indd 92 9/29/2012 12:37:20 PM