Sonic hedgehog controls growth of external genitalia by regulating cell cycle kinetics

Ashley W. Seifert, Zhengui Zheng, Brandi K. Ormerod, Martin J. Cohn

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

During embryonic development, cells are instructed which position to occupy, they interpret these cues as differentiation programmes, and expand these patterns by growth. Sonic hedgehog (Shh) specifies positional identity in many organs; however, its role in growth is not well understood. In this study, we show that inactivation of Shh in external genitalia extends the cell cycle from 8.5 to 14.4 h, and genital growth is reduced by ∼75%. Transient Shh signalling establishes pattern in the genital tubercle; however, transcriptional levels of G1 cell cycle regulators are reduced. Consequently, G1 length is extended, leading to fewer progenitor cells entering S-phase. Cell cycle genes responded similarly to Shh inactivation in genitalia and limbs, suggesting that Shh may regulate growth by similar mechanisms in different organ systems. The finding that Shh regulates cell number by controlling the length of specific cell cycle phases identifies a novel mechanism by which Shh elaborates pattern during appendage development.

Original languageEnglish
Article number23
JournalNature Communications
Volume1
Issue number3
DOIs
StatePublished - 2010

Bibliographical note

Funding Information:
We thank Drs Brian Harfe and Malcolm Maden for helpful comments and discussion. We thank Dr Brian Harfe for the gift of the ShhGFPcre and ShhCreERT2 mouse lines, Dr Andrew McMahon for the ShhC mouse line, and Eric Rubin and Heather Freiman for technical assistance. This study was supported by a grant from the NIH (1R01 HD054554 to M.J.C.) and the Howard Hughes Medical Institute (to M.J.C.).

Funding

FundersFunder number
National Institute of Environmental Health Sciences (NIEHS)R01ES017099

    ASJC Scopus subject areas

    • General Chemistry
    • General Biochemistry, Genetics and Molecular Biology
    • General Physics and Astronomy

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