Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells

Alan R. Rodrigues, Nayuta Yakushiji-Kaminatsui, Yuji Atsuta, Guillaume Andrey, Patrick Schorderet, Denis Duboule, Clifford J. Tabin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. In the early limb bud, for instance, Sonic hedgehog (Shh) is expressed in the distal posterior mesenchyme, where it acts as a mediator of anterior to posterior (AP) patterning, whereas fibroblast growth factor 8 (Fgf8) is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to distal (PD) axis. Here we use cultured limb mesenchyme cells to assess the response of the target Hoxd genes to these two factors. We find that they act synergistically and that both factors are required to activate Hoxd13 in limb mesenchymal cells. However, the analysis of the enhancer landscapes flanking the HoxD cluster reveals that the bimodal regulatory switch observed in vivo is only partially achieved under these in vitro conditions, suggesting an additional requirement for other factors.

Original languageEnglish
Pages (from-to)3139-3144
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number12
DOIs
Publication statusPublished - Mar 21 2017

All Science Journal Classification (ASJC) codes

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