QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online March 21, 2008
doi: 10.1242/10.1242/dev.018945

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, P. Articles by Werb, Z. Search for Related Content PubMed PubMed Citation Articles by Lu, P. Articles by Werb, Z. Social Bookmarking                         What's this?

The apical ectodermal ridge is a timer for generating distal limb progenitors

Department of Anatomy and Program in Developmental Biology, University of California at San Francisco, San Francisco, CA 94143-0452, USA.

^* Authors for correspondence (e-mail: pengfei.lu{at}ucsf.edu, zena.werb{at}ucsf.edu)

Accepted 11 February 2008

The apical ectodermal ridge (AER) is a transient embryonic structure essential for the induction, patterning and outgrowth of the vertebrate limb. However, the mechanism of AER function in limb skeletal patterning has remained unclear. In this study, we genetically ablated the AER by conditionally removing FGFR2 function and found that distal limb development failed in mutant mice. We showed that FGFR2 promotes survival of AER cells and interacts with Wnt/β-catenin signaling during AER maintenance. Interestingly, cell proliferation and survival were not significantly reduced in the distal mesenchyme of mutant limb buds. We established Hoxa13 expression as an early marker of distal limb progenitors and discovered a dynamic morphogenetic process of distal limb development. We found that premature AER loss in mutant limb buds delayed generation of autopod progenitors, which in turn failed to reach a threshold number required to form a normal autopod. Taken together, we have uncovered a novel mechanism, whereby the AER regulates the number of autopod progenitors by determining the onset of their generation.

Key words: Apoptosis, Autopod progenitors, Cell proliferation, FGF signaling, Limb patterning, Mouse, Wnt signaling

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. R. Manske and K. C. Oberg Classification and Developmental Biology of Congenital Anomalies of the Hand and Upper Extremity J. Bone Joint Surg. Am., July 1, 2009; 91(Supplement_4): 3 - 18. [Full Text] [PDF]

				Y. Yang and S. H. Kozin Cell Signaling Regulation of Vertebrate Limb Growth and Patterning J. Bone Joint Surg. Am., July 1, 2009; 91(Supplement_4): 76 - 80. [Full Text] [PDF]

				I. Tzchori, T. F. Day, P. J. Carolan, Y. Zhao, C. A. Wassif, L. Li, M. Lewandoski, M. Gorivodsky, P. E. Love, F. D. Porter, et al. LIM homeobox transcription factors integrate signaling events that control three-dimensional limb patterning and growth Development, April 15, 2009; 136(8): 1375 - 1385. [Abstract] [Full Text] [PDF]

				Y. Yang Growth and Patterning in the Limb: Signaling Gradients Make the Decision Sci. Signal., January 13, 2009; 2(53): pe3 - pe3. [Abstract] [Full Text] [PDF]