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Limb Development Notes

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-limb development day 24-56
-upper limbs and lower limbs formed in a similar sequence of events- (occurs earlier in the upper limb) from ectodermal and mesodermal tissue
-both upper limb and lower limb is organised into 3 regions
-stylopod (humerus and femur)
-zeugopod (ulna+radius/ tibia and fibula)
-autopod(wrist and fingers/ankle and toes)
-bones, ligaments, tendons- originate in the lateral plate mesoderm, muscle (somites), Schwann cells and melanocytes in the neural crest cells Formation of the upper and lower limb buds
-upper and lower limb buds are formed by the proliferation of the somatopleuric lateral plate mesoderm in the limb regions of the flank
-upper limb bud appears in lower cervical region- DAY 24
-Lower limb bud- lumbar region at DAY 28
-Both limb buds consist of an ectodermal cap and inner mesodermal core Limb bud outgrowth
-proliferation of somatopleuric plate in the lateral plate mesoderm. Lateral plate mesoderm secretes FGF10 and this induces overlying ectoderm to form apical ectodermal ridge. Apical ectodermal ridge secretes FGF 4 and FGF 8 which maintains FGF10 signal and induces proliferation in mesoderm.
-Fibroblast growth factor is the key signal that induces the lateral plate mesoderm to intiate limb bud formation
-beads soaked in FGF and applied to the flank of chick embryos could induce formation of limbs in the regions between the fore and hind limbs. Also loss of FGF receptor leads to inhibition of limb initiation
-FGFs are expressed in the AER. Apical ectodermal ridge
-ectoderm along the apex of the bud, induced by the somatopleuric mesoderm differentiates into the apical ectodermal ridge

-removal of the AER, stops further outgrowth of distal limb
-key role of AER is maintenance of proliferation in the distal end of limb in region known as the progress zone.
-the ectoderm covering the limb bud forms the epidermis of the skin, lateral plate mesoderm forms the skeleton, connective tissues, blood vessels of the limbs Three axes of limb buds
-formation and external shape of limps rely on patternin of mesenchymal mesodermal cells in three axes
-limb bud differentiates with respect to three axes
-proximal distal axes- defines the sequence of limb segments
-cranio-caudal- defines the differentiation from first digit side of limb to 5 th digit side
-dorsoventral-defines differentiation of extensor and flexor compartments Promximodistal limb segments
-the proximo-distal axis consists of the stylopod, zeugopod, autopod
-transplantation experiments show that the AER induces growth in the distal subridge mesoderm- PROGRESS ZONE but doesn't specifiy which part of bud will form which segment of limb
-descision is made by mesodermal core- late formed mesenchyme at tip of elongating bud forms distal segments of the limb. Early formed mesenchyme at baseof bud differentiates into proximal segments of limb after leaving the influence of AER
-evidence: transplantation experiments on chick wing buds. If a composite artificial wing bud is made by combining late formed mesenchyme from tip of older bud with ectodermal cap of any age- only distal parts of wing forms. But, if a wing bud is made using ectodermal cap of any age and early formed mesodermal core- entire limb is formed.
-evidence tells us- progress zone model: the factor that specifies which limb segment will be formed by a given zone of mesenchyme is the amount of time the mesenchyme has spent under the influence of the apical ridge- mesenchymal cells measure this time by the number of cell divisions
-The time the mesodermal cells spend in the progress zone, results in a collinear expression of two sets of genes HOX A, HOX D, Expression of specific Hox genes colinearly leads to the development of specific skeletal elements of upper and lower

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