• Mesodermal parts of limb develop from Þ somatopleure (bones, connective tissue, blood vessels); somites (muscles)
• Thus muscle cells migrate into lateral mesoderm from somites

• Positioning the Limbs along the Anterior-Posterior Axis of the Embryo (Hox Genes and FGF10)
• Intermediate mesoderm induces limb formation Þ secretes FGF10; FGF10 synthesis is directed by Hox genes
• The Apical Ectodermal Ridge Secretes FGF-4 to Pattern the Proximal-Distal Axis of the Limb
• AER = thickening of the ectoderm Þ if removed, will only form the humerus
• Allows formation of bones in normal proximal Þ distal fashion
• Graft in another AER Þ get 2 limb structures
• What is the signal? FGF-4 (made in posterior half of AER (pinky side))
• The Posterior Limb Bud Mesoderm (the ZPA) Secretes Sonic Hedgehog to Pattern the Anterior-Posterior Axis of the Limb
• ZPA = zone of polarizing activity
• secretes sonic hedgehog; patterns the ant-post axis of the limb; tells the cells in post part to become the post digits
• The Dorsal Ectoderm Secretes Wnt-7a to Pattern the Dorsal Ventral Axis of the Limb
• Dorsal ectoderm synthesizes Wnt7a
• Tells the dorsal cells to be dorsal
• Knock it out, form palm on back of hand
• FGF-4, sonic hedgehog, Wnt7a set up the axes
• Hox Genes 9 to 13 Pattern the Limb
• What are the downstream genes of these signals?
• Hox genes?; direct link from signal to Hox genes has not yet been made
• These Hox genes respond to FGF-4, sonic hedgehog, Wnt7a

• Given to pregnant women to prevent nausea
• Resulted in specific limb defects in children
• Possibly acts on the Hox genes

Tissue Between the Digits – Removed by Programmed Cell Death Induced by BMP-4

• Webbing between digits die
• Chicken feet express BMP-4 between the digits Þ duck feet don’t
• BMP-4 induces the cell death between digits
• No induction from other cells; cell induces self to die