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BIOL 1004 (106)

Limb embryology I

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BIOL 1004
Tamy Superle

Outline of Lecture 04 (01-10 B; Kotch) Limb embryology I. Timeline of limb thvelopment th - Starts in 4 week, finished by 8 week - Upper limb initiated 3-4 days before lower limb and stays ahead II. Development of the three limb axes (proximal/distal, anterior/posterior, dorsal/ventral) th A. Limb Bud initiation (end of 4 week) - Limb bud is mesenchyme covered by ectoderm - Induced by FGF8 release from intermediate mesoderm 1) FGF8 = mitogen that signals LPM to proliferate => limb bud 2) FGF8 initiates AER (Apical Ectodermal Ridge) 3) Then, FGF8 from AER stimulates growth in progress zone * Limb bud malformations often related to urogenital malformations b/c both involve intermediate mesoderm defects - Lateral plate mesoderm (somatic): bone, connective tissue, vasculature - Paraxial mesoderm (somite-derived): muscle (myotome) B. Proximal/Distal Axis - AER = apical ectodermal ridge; formed by ectodermal thickening - influences underlying mesenchyme to proliferate (progress zone) - mesenchyme furthest from AER differentiates first - Pattern of HOX genes (more distally) controls P/D differentiation - Defects (early teratogen) lead to limb truncations C. Anterior/Posterior Axis - SHH gradient produced by mesenchymal tissue (posterior aspect known as ZPA = zone of polarizing activity); controls A/P patterning - Defects lead to ectrodactyly (too few digits; AER too narrow/deficient) or polydactyly (too many digits; AER too broad) - Webbing of finger and toes removed by apoptosis - Syndactyly = soft tissue fusion between digits due to insufficient apoptosis - Defects (e.g. MSX2, BMP4) lead to syndactyly (fused digital soft tissue) * AER delineates where digits will form, ZPA & SHH determine which digits will form & where D. Dorsal/Ventral Axis - Not well understood; involves induction by ectoderm III. Bone Formation - Cells furthest from AER differentiate first - Mesenchyme differentiates into cartilage, then becomes bone by endochondral ossification - Lateral plate mesoderm condenses along long axis into cartilganous perichondrium, this model is replaced by bone - Interzones between bones will differentiation into joint tissue - Diaphyses ossified by birth (begins @ 7 week), epiphyses shortly thereafter - Continued bone growth occurs at epiphyseal growth plate IV. Muscle formation - Common The
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