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Sci. STKE, 11 November 2003
Vol. 2003, Issue 208, p. tw437
[DOI: 10.1126/stke.2003.208.tw437]


MORPHOGEN SIGNALING Hedgehog Meets the Cilia?

The secreted morphogen Hedgehog regulates patterning events in the nervous system during embryogenesis. For example, Sonic hedgehog (Shh) produced in the notochord (which arises from a structure called the node) specifies ventral cell types in the neural tube, and mice that lack functional Shh display abnormalities in the development of these cells and in neural patterning. Huangfu et al. noticed the same phenotype in three mouse mutants, wimple (wim), flexo (fxo), and Kif3a. The former two were characterized as having a mutation in alleles of genes that are homologous to those of a single-celled alga that encode intraflagellar transport (IFT) proteins required for flagella development. The latter encodes a subunit of a kinesin-II IFT motor required for nodal cilia formation. The node cells of each mutant embryo lacked all nonmotile primary cilia. Analyses of mice with multiple mutations indicated that the IFT mutations block activation of the Shh pathway downstream of its receptor, Patched, and downstream of Rab23, a vesicle transport protein that negatively regulates the signaling pathway. Though it remains unclear how three IFT proteins are required for Shh signaling in neural cells, the authors postulate that cilia could produce a signal that is required for Shh signaling. IFT proteins might also direct Gli transcription factors, which control Shh target gene expression, to locations where they could avoid proteolytic processing to repressor forms.

D. Huangfu, A. Liu, A. S. Rakeman, N. S. Murcia, L. Niswander, K. V. Anderson, Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426, 83-87 (2003). [Online Journal]

Citation: Hedgehog Meets the Cilia? Sci. STKE 2003, tw437 (2003).

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