Embryology

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Topic updated on 04/22/13 11:27am
Limb Development
  • Overview
    • the appendicular system forms between the 4-8 weeks of gestation
    • limb bud development 
      • appears to be under the control of fibroblast growth factors (FGF)
      • enlargement of the limb bud is due to the interaction between the apical ectodermal ridge (AER) and the mesodermal cells in the progress zone.  
  • Limb bud growth regions  
    • AER
      • regulates proximal to distal growth and interdigital necrosis
      • forms under FGF10 stimulation
      • secretes FGFs that act on ZPA
        • FGF8 expressed throughout AER
        • FGF4 expressed in posterior region only
          • can act as substitute for AER
    • Zone of polarizing activity (ZPA) 
      • anterior-posterior and radio-ulnar growth 
        • through Sonic hedgehog pathway
      • secretes Shh protein (key component)
  • Key Genes
    • Sonic Hedgehog (Shh) genes
      • secreted by ZPA
      • involved with HOX gene expression
      • anterior-posterior growth
        • anterior mesoderm expresses ALX4
        • posterior mesoderm expresses Hox8
      • concentration gradient dictates formation of digits
        • little finger develops where there is highest Shh concentration
        • thumb develops where there is lowest Shh concentration
      • activates Gremlin
        • Gremlin inhibits BMPs that would otherwise block FGF expression in the AER
    • Hox genes
      • anterior-posterior patterning
        • together with Shh
      • regulate somatization of the axial skeleton, essentially patterning digit formation 
    • Wnt genes (Wnt7a)
      • expressed in dorsal (non-AER) ectoderm 
      • dorsal-ventral growth
  • Mutations
    • removal of AER
      • truncated limb
    • duplication of ZPA
      • mirror-image duplication of the limb
Key Genes
Gene/Region Location Regulates
Apical ectodermal ridge (AER) ectoderm
Proximal to distal growth and interdigital necrosis
Zone of polarizing activity (ZPA) mesoderm
Anterior-posterior and radio-ulnar growth
Wnt genes ectoderm Dorso-ventral growth
Sonic hedgehog (Shh) genes mesoderm (secreted by ZPA) Antero-posterior growth
Hox genes mesoderm Antero-posterior growth
 
Spine and Spinal Cord Development
  • Somites
    • the spinal column originates from pairs of mesodermal structures known as somites 
    • somites develop in a cranial to caudal direction on either side of the notochord and neural tube
      • this process is dependent on the presence of the paraxis gene
    • somite layers
      • sclerotome  
        • layer will become the vertebral bodies and annulus fibrosus 
      • myotome
        • will lead to myoblasts
      • dermatome
        • becomes skin
  • Dorso-vental patterning
    • dorso-vental patterning of the neural tube determined by counteracting activities of
      • Sonic Hedgehog (Shh)
        • in the floor plate and notochord (ventral)  
      • canonical Wnt/β-catenin
        • in the roof plate (dorsal)  
  • Metameric shift phenomenon
    • the phenomenon of how the spinal nerves, which originally ran in the center of the sclerotome, exit between the two vertebral bodies at each level. 
  • Progression
    • neural crest 
      • forms PNS, pia mater, spinal ganglia, sympathetic trunk
    • neural tube  
      • forms spinal cord
    • notochord
      • forms anterior vertebral bodies and nucleus pulposus  
  • Ossification centers
    • vertebrae have 3 primary ossification centers
      • centrum (anterior vertebral body)
      • neural arch (posterior elements, pedicles, small portion of anterior vertebra)
      • costal element (anterior part of lateral mass, transverse process, or rib)
  • Intervertebral disc
    • nucleus pulposus forms from notochord  
    • annulus fibrosus forms from sclerotome  

 

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Qbank (3 Questions)

TAG
(OBQ10.225) Congenital unilateral transverse absence of the forearm results from vascular insult to which of the following? Topic Review Topic

1. Notochord
2. Endoderm
3. Limb bud mesoderm
4. Apical ectodermal ridge
5. Epithelial ectoderm

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TAG
(OBQ09.55) What is the function of the homeobox gene products? Topic Review Topic

1. Create cross links between collagen fibers
2. Regulate somatization of the axial skeleton
3. Stimulate calcification in the hypertrophic zone
4. Cause a mutation which stimulates cell proliferation
5. Mediate the activity of the polarizing zone

PREFERRED RESPONSE ▶
TAG
(OBQ04.187) The sclerotome of the somites develops into what mature anatomical structure? Topic Review Topic

1. Autonomic nervous system
2. Dorsal muscles
3. Ventral muscles
4. Appendicular skeleton
5. Axial skeleton

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