How does Shh end up expressed only in the posterior bit of the limb bud?What does it do once it is expressed?
Feedback between the AER and the ZPA in the forelimb bud: induction of SHH • Newly induced AER secretes FGF8 into underlying mesenchyme • Posterior limb bud mesenchyme expresses hoxb-8; FGF-8 is coming from the AER; where they overlap – induction of Shh (only in posterior) • ZPA is formed/induced; Shh maintains FGF8s’ expression in the AER and FGF8 and FGF4s maintain Shh expression… It’s more complicated: other proteins are necessary as well
Nature Reviews Genetics 4, 133-143 (February 2003) , DOI 10.1007/978-3-662-43784-1 Limb outgrowth
Digit formation : Shh-secreting cells form digits 4 and 5, and contribute to the specification of digits 2 and 3 in the mouse limb • digit I is Shh independent; • digit II possibly depends on Shh concentration (as gradient is formed); • digit III depends on Shh concentration and the duration of Shh exposure; • and digit IV and V depend on the duration of high levels of Shh signaling autocrine and paracrine exposure to Shh
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- Sonic hedgehog, limb development