HedgehogandBmpGenes Are Coexpressed at Many Diverse Sites of Cell–Cell Interaction in the Mouse Embryo

AbstractThe mouseHedgehoggene family consists of three members,Sonic, Desert,andIndian hedgehog(Shh, Dhh,andIhh,respectively), relatives of the Drosophila segment polarity gene,hedgehog(hh). All encode secreted proteins implicated in cell–cell interactions. One of these,Shh,is expressed in and mediates the signaling activities of several key organizing centers which regulate central nervous system, limb, and somite polarity. However, nothing is known of the roles ofDhhorIhh,nor of the possible function ofShhduring later embryogenesis. We have used serial-sectionin situhybridization to obtain a detailed profile of mouseHhgene expression from 11.5 to 16.5 days post coitum. Apart from the gut, which expresses bothShhandIhh,there is no overlap in the variousHhexpression domains.Shhis predominantly expressed in epithelia at numerous sites of epithelial–mesenchymal interactions, including the tooth, hair, whisker, rugae, gut, bladder, urethra, vas deferens, and lung,Dhhin Schwann and Sertoli cell precursors, andIhhin gut and cartilage. Thus, it is likely that Hh signaling plays a central role in a diverse array of morphogenetic processes. Furthermore, we have comparedHhexpression with that of a second family of signaling molecules, theBone morphogenetic proteins(Bmps), vertebrate relatives ofdecapentaplegic,a target of the Drosophila Hh signaling pathway. The frequent expression of Bmp-2, -4, and -6 in similar or adjacent cell populations suggests a conserved role for Hh/Bmp interactions in vertebrate development