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MIM.600725 7q36

Friday 18 April 2008


- Sonic Hedgehog (Shh) is a secreted protein identified genetically as an important developmental factor. Shh provides a morphogenic signal in the developing CNS, organizing the spatial patterning of cells in the midbrain and inducing proliferation of neuronal precursor cells in the developing cerebellum, neural tube and retina.

- Sonic hedgehog signaling may proceed by more than one mechanism. One signaling pathway is activated by Shh binding to Patched (Ptc-1) which releases inhibition of the GPCR Smoothened, activating the Shh signaling pathway and allowing progression through the G1 phase of the cell cycle.

- Shh can also affect progression through the G2/M transition. Patched binds to phosphorylated Cyclin B1, one component of the M-phase promoting factor (MPF), along with the kinase Cdc2. The interaction of Cyclin B1 with Patched blocks MPF activity, blocking progression through the G2/M transition.

- Shh binding leads to degradation of Ptc-1, release of Cyclin B1, and entry of the cyclin B1 into the nucleus.

- Patched acts as a tumor suppressor by blocking MPF activity. Blockade of the Hedgehog pathway by cyclopamine demonstrated the therapeutic potential of Hedgehog inhibition in the treatment of some cancers.

(From Biocarta)

- Hedgehog proteins as lipid-linked morphogens

Wnt and Hedgehog family proteins are secreted morphogens that act on surrounding cells to pattern many different tissues in both vertebrates and invertebrates.

The discovery that these proteins are covalently linked to lipids has raised the puzzling problem of how they come to be released from cells and move through tissue.

A synergistic combination of biochemical, cell biological and genetic approaches over the past several years is beginning to illuminate both the forms in which lipid-linked morphogens are released from cells and the variety of molecular and cell biological mechanisms that control their dispersal. (16364628)


- germline mutations in

  • holoprosencephaly 3 (MIM.142945)
  • ocular coloboma (MIM.120200)
  • solitary median maxillary central incisor (SMMCI)(MIM.147250)

- Proliferative signaling by Shh is involved in the development of cancer, including specific brain and skin cancers such as basal cell carcinomas.

See also

- SHH-GLI signaling pathway (SHH pathway)


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