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

Department of Biology, University of Florida, Gainesville, FL 32611, USA.
Nature Communications (Impact Factor: 11.47). 06/2010; 1(3):23. DOI: 10.1038/ncomms1020
Source: PubMed


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.

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    • "Shh is expressed in the cloacal endoderm and is required for all stages of genitourinary tract development [30], [38], [39]. Shh signaling controls cell cycle kinetics of mesenchyme [42]. It is worth noting that Six6, a homology of Six1, is directly involved in modulating cell cycle of retinal progenitor [43]. "
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