The development of the tetrapod limb involves specification of the limb field and induction of the early limb bud through FGF10 signaling. The proximal-distal axis is established by the AER, which secretes FGF8 to maintain the progress zone. The anterior-posterior axis is specified by SHH expression in the ZPA. The dorsal-ventral axis forms through Wnt7a expression on the dorsal side. Cell death regulated by BMPs then separates the digits and forms joints.
Welcome to the world of Homeotic genes. In this presentation I talk about the interesting history behind homeotic genes as to how it was discovered. Also, the various deformities in Drosophila related to mutations in homeotic genes and the characteristics of homeotic genes. I also talk about hox genes in humans and their function.
Welcome to the world of Homeotic genes. In this presentation I talk about the interesting history behind homeotic genes as to how it was discovered. Also, the various deformities in Drosophila related to mutations in homeotic genes and the characteristics of homeotic genes. I also talk about hox genes in humans and their function.
Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances
cell lineage , cell fate - diverse class of cell fate, cell fate in plant meristem, mammalian development cell fate, nutritional effects on epigenetics, epigenetics of plants,
control of cell fate.
Introduction
About Drosophila
Genome of Drosophila
Life cycle
Differentiation
Development of Drosophila
* Embryonic development
* Dorsal -ventral and
* Anterior posterior development
* Body segmentation
* Homeotic gene
Conclusion
Reference
Mitochondrial biogenesis is the process by which cells increase mitochondrial numbers. It was first described by John Holloszy in the 1960s, when it was discovered that physical endurance training induced higher mitochondrial content levels, leading to greater glucose uptake by muscles. Mitochondrial biogenesis is activated by numerous different signals during times of cellular stress or in response to environmental stimuli, such as aerobic exercise.
The delivery of newly synthesized protein to their proper cellular destination, usually referred to as protein targeting or sorting.
The mode of protein transport depends chiefly on the location in the cell cytoplasm of the polysomes involved in protein synthesis.
There are two modes of protein sorting:-
1) Co - translational Transportation.
2) Post - translational Transportation.
hox genes and its role in development both in human and drosophila . homeotic genes. homeobox genes. developmental biology. different types of homeotic genes in drosophila and human. deficiencydiseases due to lack of hox genes in human
Development of the Tetrapod Limb
WEL COME TO LOVYANSH LIFESCIENCE
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Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances
cell lineage , cell fate - diverse class of cell fate, cell fate in plant meristem, mammalian development cell fate, nutritional effects on epigenetics, epigenetics of plants,
control of cell fate.
Introduction
About Drosophila
Genome of Drosophila
Life cycle
Differentiation
Development of Drosophila
* Embryonic development
* Dorsal -ventral and
* Anterior posterior development
* Body segmentation
* Homeotic gene
Conclusion
Reference
Mitochondrial biogenesis is the process by which cells increase mitochondrial numbers. It was first described by John Holloszy in the 1960s, when it was discovered that physical endurance training induced higher mitochondrial content levels, leading to greater glucose uptake by muscles. Mitochondrial biogenesis is activated by numerous different signals during times of cellular stress or in response to environmental stimuli, such as aerobic exercise.
The delivery of newly synthesized protein to their proper cellular destination, usually referred to as protein targeting or sorting.
The mode of protein transport depends chiefly on the location in the cell cytoplasm of the polysomes involved in protein synthesis.
There are two modes of protein sorting:-
1) Co - translational Transportation.
2) Post - translational Transportation.
hox genes and its role in development both in human and drosophila . homeotic genes. homeobox genes. developmental biology. different types of homeotic genes in drosophila and human. deficiencydiseases due to lack of hox genes in human
Development of the Tetrapod Limb
WEL COME TO LOVYANSH LIFESCIENCE
I HAVE EXPLAIN THIS TOPIC IN DETAILS ON YOUTUBE
MY YOUTUBE CHANNEL LINK
https://youtu.be/o1h68DJ8vCg
PLEASE SHARE , LIKE
& COMMENTS FOR MORE SUCH VIDEOS
coordinated movements of gastrulation begin. This dramatic process t.pdfarjunchetri1
coordinated movements of gastrulation begin. This dramatic process transforms the simple
hollow ball of cells into a multilayered structure with a central gut tube and bilateral
symmetry.many of the cells on the outside of the embryo are moved inside it. Subsequent
development depends on the interactions of the inner, outer, and middle layers of cells thus
formed: the endoderm on the inside, consisting of the cells that have moved into the interior to
form the primitive gut; the ectoderm on the outside, consisting of cells that have remained
external; and the mesoderm between them, consisting of cells that detach from the epithelium to
form a more loosely organized embryonic connective tissue.
eventual pattern of muscles-in the limbs, for example-is determined by the routes that the
migrant cells follow and the selection of sites that they colonize. The embryonic connective
tissues form the framework through which the myoblasts travel and provide signals that guide
their distribution. No matter which somite they come from, myoblasts that migrate into a
forelimb bud will form the pattern of muscles appropriate to a forelimb, and those that migrate
into a hindlimb bud will form the pattern appropriate to a hindlimb.
Limb formation results from series of epithelial-mesenchymal inductions between the
mesenchymal cells of the lateral plate mesoderm and the overlying ectodermal cells. Cells from
the lateral plate mesoderm and the myotome migrate to the limb field and proliferate to create the
limb bud. The lateral plate cells produce the cartilaginous and skeletal portions of the limb while
the myotome cells produce the muscle components. The lateral plate mesodermal cells secrete a
fibroblast growth factor (FGF7 andFGF10, presumably) to induce the overlying ectoderm to
form an important organizing structure called the apical ectodermal ridge(AER).The AER
reciprocatively secretes FGF8 and FGF4 which maintains the FGF10 signal and induces
proliferation in the mesoderm.[citation needed] The position of FGF10 expression is regulated
by Wnt8c in the hindlimb and Wnt2b in the forelimb. The forelimb and the hindlimb are
specified by their position along the anterior/posterior axis and possibly by two T-box containing
transcription factors: Tbx5 and Tbx4, respectively.
DKK1 activation in osteoblasts is the underlying cause of glucocorticoid- and estrogen
deficiency–mediated osteoporosis, and at least partially underlies the teratogenic effects of
thalidomide on limb development.
both thalidomide-induced PCD and limb deformities could be partially inhibited by blocking
Dkk1 or activating Wnt signaling downstream of the ligand-receptor interaction
Solution
coordinated movements of gastrulation begin. This dramatic process transforms the simple
hollow ball of cells into a multilayered structure with a central gut tube and bilateral
symmetry.many of the cells on the outside of the embryo are moved inside it. Subsequent
development depends on the interactions .
What data indicate that all three germ layers are specified in the b.pdfherminaherman
What data indicate that all three germ layers are specified in the blastula? What are the
differences between dorsal and ventral mesodermal derivatives and what cellular interactions are
required for their specification?
Solution
Three germ layers of amphibians are specified in the blastula is determined by isolating these
tissues in vitro, and they are able to form into specific germ layers. The animal pole cap cells
make ectoderm, marginal region cells make mesoderm, and vegetal cells make endoderm.
Theyare specified but not determined. It is also interesting to note that if animal cap cells are
place co-cultured with vegetal cells, the animal cap cells with become mesoderm. This indicates
that vegetal cells induce other cells to form mesoderm. Experiment paired animal cap cells in 4
different sections of vegetal blastomeres to see if they induce different dorsal-ventral
mesodermal fates. Result showed that different sections of vegetal blastomere have specific
inductive capacities, which is crucial for dorsal-ventral mesoderm determination. Difference
between dorsal and ventral mesoderm derivatives: dorsal mesoderm is the notochord and somite.
In all bilaterian animals, the mesoderm is one of the three primary germ layers in the very early
embryo. The other two layers are the ectoderm (outside layer) and endoderm (inside layer), with
the mesoderm as the middle layer between them.
The mesoderm forms mesenchyme, mesothelium, non-epithelial blood cells and coelomocytes.
Some of the mesoderm derivatives include the muscle (smooth, cardiac and skeletal), the
muscles of the tongue (occipital somites), the pharyngeal arches muscle (muscles of mastication,
muscles of facial expressions), connective tissue, dermis and subcutaneous layer of the skin
At mid-blastula two signaling centers are present on the dorsal side: The prospective
neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal
endoderm secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed
at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and
further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal
organizer, and another set of secreted antagonists is produced ventrally under the control of
BMP4. The early dorsal -Catenin signal inhibits BMP expression at the transcriptional level and
promotes expression of secreted BMP antagonists in the prospective central nervous system
(CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required
for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulin-like growth factor)
signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires
mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple
signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates
Smad1 transcrip.
1. The places where limbs emerge from the body axis depend upon Hox gene expression.
2. The specification of the limb field into a hindlimb or forelimb bud is determined by Tbx4 and
Tbx5 expression.
3. The proximal-distal axis of the developing limb is determined by the induction of the ectoderm at the dorsal-ventral boundary to form the apical ectodermal ridge (AER). This induction is caused by an FGF, probably FGF10. The AER secretes FGF8, which keeps the underlying mesenchyme proliferative and undifferentiated. This mesenchyme is called the progress zone.
4. As the limb grows outward, the stylopod forms first, then the zeugopod, and the autopod is formed last. Each of these phases involves the expression of Hox genes, and the formation of the autopod involves a reversal of Hox gene expression that distinguishes fish fins from tetrapod limbs.
5. The anterior-posterior axis is defined by the expression of Sonic hedgehog in the posterior mesoderm of the limb bud. This region is called the zone of polarizing activity (ZPA). If the ZPA or Sonic hedgehog-secreting cells or beads are placed in the anterior margin, they establish a second, mirror-image pattern of Hox gene expression and a corresponding mirror-image duplication of the digits.
6. The ZPA is established by the interaction of FGF8 from the AER and mesenchyme made competent to express Sonic hedgehog by its expression of particular Hox genes. Sonic hedgehog acts, probably in an indirect manner, to change the expression of the Hox genes in the limb bud.
A Review on Genetic Dominant Disorder-Polydactylyijtsrd
Polydactyly is genetic disorder in which there is mutation of gene that is located on short arm of chromosome 7. One gene that can cause polydactyly is GLI3 and it is one among number of genes that are known to be involved in the patterning of tissues and organs during development of the embryo. Mutations of GLI3 gene during development will cause two types of polydactyly. Those are postaxial ulnar and preaxial radial polydactyly. The treatment plan is based on the outcome of analysis of patients medical history, social history, motivation, social and psychological disturbance. Akshata. B. Kichadi | Dr. Uma B Gopal | Santhosh Singarapu | Chaitra. S | Manukrishnan. K | Jeevankumar. Giri "A Review on Genetic Dominant Disorder-Polydactyly" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd20232.pdf
Paper URL: https://www.ijtsrd.com/medicine/anatomy/20232/a-review-on-genetic-dominant-disorder-polydactyly/akshata-b-kichadi
What are cytoplasmic determinants What is the relevance of the yell.pdfartimagein
we are interested in comparing the mean costs of electrical energy produced by nuclear and coal
powered electrical power plants. Pilot studies have indicated the variation in the costs associated
with the two types of plants are sn= $.224 and sc= $ .20.How many plants of each type should be
sampled in order to estimate the difference mean costs with a 95% confidence interval to within
$.01?
Solution
sn = 0.224 and sc = 0.20
Let sample sizes be n1 and n2
SE = 0.224/rtn1 + 0.20/rtn2
Margin of error = z alpha/2 (SE)
For 95% z = 1.96
Hence 1.96(0.224/rtn1 + 0.20/rtn2) = 0.01
As there is one equation and two variables assume n1 = n2
Then we have
0.424/rtn1 = 0.01/1.96 = 0.0051
Or rt n1 = 8.313
n1 =69.111
or n >70 for each sample..
In this PPT I completed that interesting topic , molecular embryology discussing this time molecular regulation of some other systems in the developing embryo, wishing that I could make this as simple as possible.
In this PPT I completed that interesting topic In this PPT I completed that interesting topic , molecular embryology discussing this time molecular regulation of some other systems in the developing embryo, wishing that I could make this as simple as possible.
Genetics & malocclusion /certified fixed orthodontic courses by Indian dent...Indian dental academy
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Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
00919248678078
Genetics & malocclusion /certified fixed orthodontic courses by Indian denta...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
00919248678078
This PPT is a simplified introduction for molecular embryology. It includes molecular regulation of Heart, GIT, Liver, Pancreas, Kidney and somites Development. This will be followed by another PPT with molecualr regulation of other important organs as Brain and spinal cord. I hope that I could make it as simple as possible, waiting for your valuable comments. Enjoy my dear friends.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
2. PATTERN FORMATION
process by which embryonic cells form
ordered spatial arrangement of
differentiated tissues.
How is it that the embryo is able not only
to generate all the different cell types of
the body but also to produce them in a
way that forms functional tissues and
organs.
2
4. Many recent studies show that the basic
morphogenetic rules for forming a limb appear to
be the same in all tetrapods.
Fallen & Crosby (1997) showed that grafted
pieces of reptile/mammalian limb buds can
direct the formation of chick limbs
Sessions et al (1989) found that regions of
frog limb buds can direct the patterning of
salamander limbs and vice versa.
4
5. Development of the tetrapod limb has to function
in a three-dimensional coordinated system
Proximal-distal axis------ Fibroblast Growth
Factor family protein and Hox Genes
Anterior-posterior axis----- Sonic hedgehog
protein
Dorsal-ventral axis------ Wnt7a protein
5
6. 1. Formation of the Limb Bud
2. Generating the Proximal- Distal Axis of the
Limb
3. Specification of Anterior- Posterior Limb Axis
4. Generation of the Dorsal- Ventral Axis
5. Cell Death and the Formation of Digits and
Joints
6
DEVELOPMENT OF THE TETRAPOD LIMB
7. 1. LIMB BUD FORMATION
1.A Limb Field Specification
regulated by Hox Genes
and Retinoic Acid
Limb field position is determined with
respect to the level of Hox gene expression
along the anterior –posterior axis
Retinoic acid is also
critical in limb bud
outgrowth. 7
8. 1.B INDUCTION OF EARLY LIMB BUD:
FIBROBLAST GROWTH FACTORS
• Limb muscle precursors +
limb skeletal precursors-----
LIMB BUD
• Signal for limb bud
formation comes from the
lateral plate mesoderm cells
that later will become
PROSPECTIVE LIMB
MESENCHYME CELLS
•FGF10 = capable of initiating
the limb –forming interactions
between ectoderm and
mesoderm.
8
10. 1.C SPECIFICATION OF FORELIMB OR
HINDLIMB: TBX4 AND TBX5
The gene encoding the Tbx5 transcription factor is
transcribed in forelimbs of embryo while the gene
encoding the Tbx4 transcription factor is expressed
in hindlims.
10
12. 2. GENERATING THE PROXIMAL –DISTAL AXIS
OF THE LIMB: FIBROBLAST GROWTH FACTOR
& HOX GENES
AER (Apical Ectodermal Ridge)--- major signaling center for
the developing limb
• maintaining the mesenchyme
beneath it in a plastic, proliferating
phase that enables the proximal-distal
growth of the limb
•Maintain the expression of molecules
that generate anterior-posterior axis
•Interacting with the proteins
specifying the anterior-posterior and
dorsal-ventral axes so that each cell is
given instructions on how to
differentiate.
12
13. THE PROGRESS ZONE (PZ)
13
Molecules that are
secreted from AER
(FGF8) keep the PZ
mesenchyme cells
dividing.
14. AER NECESSARY FOR LIMB BUD
OUTGROWTH
Removal of AER at various times prematurely truncates limb
14
15. 15
HOX GENES AND THE
SPECIFICATION OF THE PROXIMAL-
DISTAL AXIS
PROXIMAL DISTAL
POSTERIOR
ANTERIOR
16. 16
3. SPECIFICATION OF THE ANTERIOR-
POSTERIOR LIMB AXIS: SONIC
HEDGEHOG PROTEIN
Zone of Polarizing Activity
(ZPA) --- block of
mesodermal tissue near the
posterior junction of the
young limb bud.
17. 17
SONIC HEDGEHOG IS EXPRESSED IN
ZPA
SHH works by initiating and sustaining a cascade of other proteins,
such as BMP2 and BMP7. A gradient of BMPs expressed from
ZPA specify the digits.
However, transplantation of ZPA to the anterior portion of limb
bud leads to the formation of mirror-image digit pattern.
18. 4. GENERATION OF THE DORSAL-
VENTRAL AXIS: WNT7A
18
• Wnt7a gene is expressed
only in dorsal portion of
limb bud.
• It induces activation of
the Lmx1 gene in dorsal
mesenchyme and this gene
encodes a transcription
factor that appears to be
essential for specifying
dorsal fates in the limb.
19. 5. CELL DEATH AND THE FORMATION
OF DIGITS AND JOINTS
19
• Signal for apoptosis in the autopod
region is provided by the Bone
Morphogenetic Proteins.
• BMP2, BMP4 and BMP7 are each
expressed in the interdigital mesenchyme
•Nogging proteins supressed BMPs
•Noggin proteins is synthesized in
developing digits.and perichondrial cells
surrounding them.
•However Blocking BMP signaling
between digits prevents interdigital
apoptosis.
20. FORMING JOINTS
20
• Bone Morphogenetic Proteins
are responsible in forming
joints.
•BMP7 is synthesized in the
perichondrial cells sorrounding
the condensing chondrocytes
and promotes cartilage
formation.
•Other BMPs, BPM2 and GDF5,
are expressed at the regions
between the bones, where joints
will form.
21. SUMMARY: THE DEVELOPMENT OF
TETRAPOD LIMB
The places where limbs emerge from the body axis
depend upon Hox gene expression.
The specification of the limb field into a hindlimb or
forelimb bud is determined by Tbx4 and Tbx5
expression.
The proximal-distal axis of the developing limb is
determined by the induction of the ectoderm at the
dorsal-ventral boundary to form the apical
ectodermal ridge (AER). This induction is caused by
an FGF10. The AER secretes FGF8, which keeps the
underlying mesenchyme proliferative and
undifferentiated. This mesenchyme is called
progress zone
21
22. SUMMARY: THE DEVELOPMENT OF
TETRAPOD LIMB
As the limb grow outward, the stylopod forms first, then
the zeugopod, and the autopod is fomed last. Each of
these phases involves the expression of Hox genes, and
the formation of the autopod involves a reversal of Hox
gene expression that distinguishes fish fins from
tetrapod limbs
The anterior-posterior axis is defined by the expression
of Sonic hedgehog in the posterior mesoderm of the limb
bud. This region is called the zone of polarizing activity
(ZPA). If the ZPA or Sonic hedgehog-secreting cells or
beads are placed in the anterior margin, they establish a
second, mirror-image pattern of Hox gene expression and
a corresponding mirror-image duplication of the digits
22
23. SUMMARY: THE DEVELOPMENT OF
TETRAPOD LIMB
The ZPA is established by the interaction of FGF8
from the AER and mesenchyme made competent to
express Sonic hedgehog by its expression of
particular Hox genes. Sonic hedgehog acts, probably
in an indirect manner, to change the expression of
Hox genes in the limb bud
23
24. SUMMARY: THE DEVELOPMENT OF
TETRAPOD LIMB
The dorsal-ventral axis is formed, in part, by the
expression of Wnt7a in the dorsal portion of the
limb ectoderm. Wnt7a also maintains the expression
of Sonic hedgehog in the ZPA and FGF4 in the
posterior AER. FGF4 and Sonic hedgehog
reciprocally maintain each other’s expression.
Cell death in the limb is necessary for the formation
of digits and joints. It is mediated by BMPs. The
effects of BMPs can be regulated by the Noggin
protein and the BMPs can be involved both in
inducing apoptosis and in differentiating the
mesenchymal cells into cartilage 24
Editor's Notes
Good morning class. For today I’ll be discussing the Development of the tetrapod limb.
By the way, tetrapods are four footed or four-limbed animals or vetebrates. One example are us humans and mostly mammals.
Let us have a brief introduction.
One of the most dramatic properties of developing organisms is the PATTERN Formation. And PATTERN FORMATION is the process by which embryonic cells form ordered spatial arrangement of differentiated tissues. Or it is the generation of complex organizations of cell fates in space and time.
So in this process, one question usually ask is how is it that the embryo is able not only to ….. . . . . . . .
Let’s find out as we go deeper to this chapter.
Let us have a brief review on the different parts and regions of the tetrapod limb.
Vertebrate limb is an extremely complex organ with an asymmetrical arrangement of parts.
When we say ASSYMETRICAL the 2 sides or 2 halves of an organ or organism are not the same in terms of their morphology.
There are 3 main axes to consider in vertebrate limb.
One of which is the PROXIMAL-DISTAL axis or the shoulder to finger in forelimbs and the hip to toe in hindlimbs
The second is the ANTERIOR-POSTERIOR axis or the thumb to pinky axis.
Third is the DORSAL-VENTRAL axis or the knuckle and palm axis.
The bones of the limb, be it wing flippers foot or hand consist of 3 regions
First is the PROXIMAL STYLOPOD region consist of the humerus bone in forelimb or femur bone in hindlimb
Second is the middle region the ZEUGOPOD consist of radius and ulna for forelimb or tibia and fibula bones for hindlimb
And the third region is DISTAL AUTOPOD consists of carpals and fingers in forelimb and tarsals and toes in hindlimb.
Many researchers…….
In the work of Fallen and Crosby they Were able to shoW that the ………………………..
Development of the tetrapod limb has to function ……………….
When We say 3-dimensional cordinated system the 3 axes of the vertebrate limb are all interrelated and coordinated. The formation or development of one axis mutually supports the formation of the other 2 axis.
We Will be discussing the coordination of these 3 axes later.
Researchers Were able to identify particular proteins and genes that play a role in the formation of the 3 axes
The proximal-distal axis appears to be regulated by fibroblast groth factor family protein
The anterior-posterior axis seems to be regulated by sonic hedgehog protein
The dorsal-ventral axis is regulated by Wnt7a protein
Here is the outline of the Whole Tetrapod Limb Development
First is the formation of the limb bud…………………..
Let us proceed to the first process, the LIMB BUD FORMATION
There are 4 limb buds per embryo and they are located opposite to each other With respect to the midline
The first step in limb bud formation is the LIMB FIELD SPECIFICATION and it is regulated by HOX GENES and retinoic acid
By the Way Limb field is Where limb bud Will emerge.
Limb field position is determined…….
And also retinoic acid is critical in limb bud outgroWth since blocking OF Retinoic acid Synthesis prevents limb bud initiation
After limb field specification, INDUCTION OF EARLY LIMB BUD folloWs and it begins When mesenchyme cells such limb muscle precursors and limb skeletal precursors proliferate and accumulate underneath epidermal tissue creating a circular bulge called limb bud.
Recent studies on the earliest stage of limb formation have shoWn that the signal for limb bud formation……..
And this PROSPECTIVE LIMB MESENCHYME CELLS secrete the paracrine factor FGF10
And this FGF10 is capable of……………
In this experiment, beads containing fgf10 are placed ectopically beneath the flank ectoderm and then extra limb emerges.
Thus, fgf10 is responsible in Induction of early limb bud.
Any question? If none let us proceed hahaa
The next process is the Specification of forelimb or hindlimb
The limb buds have to be specified as being a forelimb or a hindlimb.
So hoW are this distinguised?
There are a lot of researches conducted to ansWer this question. And they all agreed to only one correlation and it says that……..
Many researchers like Ohuchi et al, Logan et al, Takuchi et al and Rodriguez-Esteban et al provided a GAIN OF FUNCTION EVIDENCE that Tbx4 and Tbx5 specify hindlimb and forelimb respectively.
So in this experiment this bud induced by placing bead containing fgf10 close to the forelimb portion expressed Tbx5 and become forelimb.
In this bud induced by placing FGF bead near to the hindlimb portion expressed Tbx4 and developed as hindlimb
And those bud induced by placing FGF bead at the center or at the boundary of forelimb and hindlimb portion expressed Tbx5 anteriorly and Tbx4 posteriorly forming a chimeric structure With anterior resembling forelimb and posterior portion resembling hindlimb.
Thus Tbx4 and Tbx5 appear to be critical in instructing the limbs to become hindlimb and forelimb respectively.
Let us move on to the 2nd stage of limb development; the generation of the proximal-distal axis.
As mesenchyme cells enter the limb region they secrete factors that induce the overlying ectoderm to form a stucture called APICAL ECTODERMAL RIDGE.
This ridge runs along the distal margin of limb bud and Will become the major signalling center for the dev…….
It has a lot of function that explains Why limb development is a 3-dimensional coordinated system.
It maintains the mesenchyme……..
…
…
So apical ectodermal ridge has contributions in forming the 3 axes of the limb.
The proximal-distal axis is defined only after the induction of the apical ectodermal ridge by the underlying mesoderm.
The limb bud elongates by means of proliferation of the mesenchyme cells underneath the AER. This region of cell division is called the PROGRESS ZONE and it extends about 200 micrrometer from AER.
Molecules that are secreted from AER ……..
When AER is removed from an early limb bud, only most proximal parts are made.
As shoWn in letter B picture, AER is removed after Stylopod formation and only humerus bone is developed.
And here in letter D, AER is removed during the development of zeugopod or middle region of limb, only humerus and ulna bone are developed.
Thus (effects click) Removal of AER at vaious times prematurely truncates/shortens limb.
The type of structure formed along the proximal-distal axis is specified by the Hox genes.
A While ago We mention that hox genes played a role in specifying the place Where the limbs ill form of the specification of limb.
No they Will play a second important role in specifying Wether a particular mesenchymal cell Will become stylopod,zeugopod or autopod
The mechanism by Which Hox genes could specify the proximal-distal axis is not yet fully understand but it thought that as limb bud groWs outWard, the pattern of hox gene expression changes.
When the stylopod is forming Hoxd-9 and Hoxd-10 are expressed in the Progress Zone mesenchyme.
When the zeugopod bones are being formed, the pattern of hox gene expression shifts remarkably. The posterior portion expresses all the Hoxd genes from Hoxd9 to 13 While only Hoxd-9 is expressed anteriorly.
When autopod is forming there is a further redeployment of Hox gene expression. Hoxd-9 is no longer expressed rather Hoxa 13 and Hoxd 13 is expressed anteriorly While throughout the 2/3 of posterior portion hoxa 12 13 and Hoxd 10 11 12 and 13 are expressed.
Let us proceed to the third stage of limb development process; the specification of the Anterior-Posterior limb axis
The anterior-posterior Limb axis is specified by a small block of mesodermal tissue ………….
This region of the mesoderm has been called the ZONE OF POLARIZING ACTIVITY.
Through research studies they found out that the molecules conferring this ppolarizing activity on the ZPA is the SONIC HEDGEHOG protein.
Sonic hedgehog Works by ……………
HoWever, …………
(take note that the normal induction of ZPA occurs only in posterior portion)
Because this transplanted ZPA here in anterior portion duplicates the expression of Hox genes responsible in forming digits thus creating a mirror image digit structure.
One molecule that appears to be particularly important in specifying the dorsal-ventral polarity is Wnt7a.
……………………..
……………….
Research conducted by Parr and McMahon, they genetically deleted Wnt7a from mouse embryo. The resulting embryo had sole pads or ventral portion on both surfaces of their pas, showing that Wnt7a is needed for the dorsal patterning of the limb.
……………………..
……………………….
These BMPs are expressed throughout the Progress Zone mesenchyme. So hoW digits are formed When BMPs are expressed throughout PZ?
The suprression of BMPs come fom the Noggin proteins Which is synthesized in developing digits……………
……………………… that Will result to Webbed feet or hands.