Special Issue Patterns & Phenotypes
Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen
Article first published online: 20 APR 2011
Copyright © 2011 Wiley-Liss, Inc.
Special Issue: Special Issue on Limb Development
Volume 240, Issue 5, pages 1303–1310, May 2011
How to Cite
Zhu, J. and Mackem, S. (2011), Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen. Dev. Dyn., 240: 1303–1310. doi: 10.1002/dvdy.22637
- Issue published online: 20 APR 2011
- Article first published online: 20 APR 2011
- Manuscript Accepted: 21 MAR 2011
- Center for Cancer Research, National Cancer Institute, NIH
- Sonic hedgehog;
- limb development;
- digit patterning
Sonic hedgehog (Shh) controls the number and type of digits formed. Using a conditional genetic approach for timed removal of Shh, we previously proposed a biphasic model of Shh function: a transient patterning phase, during which digit progenitors are specified, and an extended proliferative phase, during which expansion of progenitor pools enables digit formation. Other models favor a close integration of digit patterning and expansion, with sequential promotion to more posterior identity over time, apparently supported by some mutants with selective posterior digit loss. To further test these models, we analyzed the dynamics of Shh activity in several oligodactylous mutants with different types of digit loss. The profile of Shh activity and phenotypic outcome in these mutants supports a biphasic over an integrated temporal model. Eomesodermin expression, as an independent marker of posterior digit identity, confirmed that proper digit 4 specification requires only the transient phase of Shh activity. Developmental Dynamics 240:1303–1310, 2011. © 2011 Wiley-Liss, Inc.