Lecture Details

Paul McMenamin; Week 1 MED1022; Anatomy

Lecture Content

Period of vulnerability for limb development is weeks 5-8, 12.9/100k are affected. Mutation of patterning genes will result in limb abnormalities, for example syndactyly (abnormal numbers of fingers) is caused by HoxD13. Reduction can be partial (meromelia) or whole (amelia). Duplication is extra defects (polydactyly). Dysplasia (malformation) can be caused by fusion syndactyly. Phocomelia is dysmelia of the limbs causing them to be short or ill-formed, caused mostly by thalidomide but can also be genetic. Hemimelia is stunting of distal segments. Adactyly is absence of all digits.

Stylopod is humerus/femur, zeugopod is radius/ulna and tibia/fibula, autopod is carpals/MC/phalanges; tarsals/MT/phalanges. Upper limb buds develop at day 24, lower limb buds at day 28. FGF-8 is expressed in the apical ectodermal ridge during limb outgrowth, two for upper limb and two for lower limb. AER runs along free edge in coronal plane from cranial to caudal. It acts on the core of the mesenchyme and proliferation and differentiation takes place beneath the ridge. The earliest mesenchyme forms the proximal segments. The limb bud has ectodermal covering, core of mesenchyme is derived from somatopleuric lateral plate mesoderm.

Mesenchyme is embryonic undifferentiated connective tissue made of stellate like fibroblast cells in a jelly-like extracellular matrix. Lateral plate mesoderm is somatopleuric, makes tendons, ligaments, connective tissue and bone. Somitic mesoderm (para-axial) migrates into the limb as dorsal and ventral masses, differentiates into muscle. Dorsal is extensors/supinator/abductors; ventral is flexors/pronators/adductors. Neural crest cells give rise to spinal ganglia, Schwann cells, melanocytes.

Differentiation of limbs occurs in week 5-8, each upper limb starts as an elongation with discernable parts separated by bends with digital plate. Tbx4 encodes forelimbs, Tbx5 encodes hindlimbs. Zone of polarising activity specifies pattern along the anterior-posterior axis. Sonic hedgehog mediates the activity of the ZPA. Inhibition of bone morphogenic protein creates webbed digits.

Limb innervation is segmental, upper limbs C5-8 (C5-T1 nerves), lower limbs L3-5 (L4 to S3 nerves)..

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