APPENDIX SIX - Signal Transduction Pathways: Hedgehog, Decapentaplegic, and Wingless

Summary

Three of the 5 chief transduction pathways used by discs are outlined below and diagramed in Figure 5.6. The other two cardinal pathways–Notch and EGFR–are discussed in Chapters 2 (Fig. 2.2) and 6 (Fig. 6.12), respectively. Abbreviations: “MF” (morphogenetic furrow), “vh” (vertebrate homolog).

Hedgehog signaling pathway (see for overview). Although the agents below constitute the standard version of this pathway, notable deviations have been found. However, the heretical proposal that Hh controls target genes in Bolwig's organ without employing Cubitus interruptus has been refuted. Aside from the components below, the zinc-finger protein Combgap regulates the levels of Cubitus interruptus in leg, wing, and eye discs but acts in the Wingless pathway in optic lobes. Another possible player is oroshigane (unknown role), which acts upstream of patched. Other genes have been implicated (e.g., shifted), but how their products fit into the chain remains to be determined.

Hedgehog (Hh, named for the lawn of spiky denticles in LOF embryos) is a 471-a.a. polypeptide (nascent form) that cleaves itself (between residues 257 and 258) into C- and N-terminal moieties: “Hh_C” bears the catalytic active site, whereas “Hh_N” is the signaling fragment. Hh_C is soluble.