Hedgehog Signaling

Supporting information

The Hedgehog (Hh) signaling pathway is crucial in the development of all known animals. In the embryo, it regulates morphogenesis of a variety of tissues and organs; in the adult, it controls stem cell proliferation.

There are three human Hh proteins: Sonic hedgehog (Shh), Desert hedgehog (Dhh) and Indian hedgehog (Ihh). Each is expressed at different times of development and in specific cell types and they are tightly controlled by highly complex, yet divergent transcriptional enhancers. Hh protein release and diffusion is controlled by various proteins including Skinny hedgehog (Sit), Dispatched (Disp), Tout-velu (Ttv) and Hedgehog-interacting protein (Hip). Hh proteins bind to the twelve transmembrane domain protein, Patched (Ptc). In the absence of Hh proteins, Ptc catalytically inhibits Smo. Hh-Ptc binding results in loss of Ptc activity and activation of Smo, which transduces the Hh signal to the cytoplasm. This leads to the activation of the Ci/Gli family of transcription factors, through complex interactions of Costal2 (Cos2), Fused (Fu) and Suppressor of fu [Su(fu)]. Furthermore, PKA, CK1, GSK-3 and Slimb modulate this signal transduction pathway.

Aberrant activation of the Hh pathway has been linked to multiple types of human cancer, particularly basal cell carcinoma. Disruption of Hh signaling during embryonic development, either through congenital mutation or maternal teratogen consumption, can lead to severe developmental disorders such as holoprosencephaly.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Shh Human SHH NM_000193 Q15465
Mouse Shh NM_009170 Q62226
Rat Shh NM_017221 Q63673
Dhh Human DHH NM_021044 O43323
Mouse Dhh NM_007857 Q61488
Rat Dhh XM_343327 Q9WUP6
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Literature for Hedgehog Signaling

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