AI Article Synopsis
- - Foxh1 is a partner to Smad proteins that helps regulate gene expression in early development, but specific targets of Foxh1 are not well understood.
- - Researchers developed a method to identify Foxh1 targets across the genome, focusing on conserved enhancers and identifying several key genes involved in embryonic development, including Hesx1 and Fgf8.
- - The study found that Foxh1 is essential for creating a transcriptional network in the developing brain and is crucial for the expression of genes involved in retinoic acid synthesis, which is important for forebrain development.
Article Abstract
Foxh1, a Smad DNA-binding partner, mediates TGFbeta-dependent gene expression during early development. Few Foxh1 targets are known. Here, we describe a genome-wide approach that we developed that couples systematic mapping of a functional Smad/Foxh1 enhancer (SFE) to Site Search, a program used to search annotated genomes for composite response elements. Ranking of SFEs that are positionally conserved across species yielded a set of genes enriched in Foxh1 targets. Analysis of top candidates, such as Hesx1, Lgr4, Lmo1, Fgf8, and members of the Aldh1a subfamily, revealed that Foxh1 initiates a transcriptional regulatory network within the developing anterior neuroectoderm. The Aldh1a family is required for retinoic acid (RA) synthesis, and, in Foxh1 mutants, expression of Aldh1a1, -2, and -3 and activation of a RA-responsive transgenic reporter is abolished in anterior structures. Integrated mapping of a developmental transcription factor network thus reveals a key role for Foxh1 in patterning and initiating RA signaling in the forebrain.
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| http://dx.doi.org/10.1016/j.devcel.2008.01.004 | DOI Listing |
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