Sonic hedgehog (SHH)
  • Involved in patterning along anterior-posterior axis
  • Embryonic development of limbs, somites, gut formation and establishment of midline CNS
    • produced in zone of polarizing activity (ZPA: collection of mesoderm cells at posterior border of apical ectodermal ridge on developing limb)
    • secreted by notochord to control neural tube patterning
  • Mutation in SHH pathway and/or haploinsufficiency can lead to Holoprosencephaly, a developmental defect characterized by a failure of the early forebrain vesicle to divide into distinct halves 
  • Necessary for proper organization along dorsal-ventral axis
  • Development of midbrain and limb patterning
    • produced at dorsal apical ectodermal ridge (AER: thickened ectoderm at distal end of each developing limb)
  • Stimulates mitosis and differentiation of underlying mesoderm
    • provides for lengthening of limbs by maintainingprogress zone (progress zone: proliferating mesenchymal cells proximal to AER)
    • produced at apical ectodermal ridge
  • Controls anterior-posterior neural tube patterning
  • Plays a role in somite segmentation, angiogenesis, and axon growth
Homeobox (HOX)
  • Involved in segmental organization in cranio-caudal direction
    • production depends on combinatorial expression of SHH, WNT-7, and FGF

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