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

Abstract

The mouse Hedgehog gene family consists of three members, Sonic, Desert, and Indian hedgehog (Shh, Dhh, and Ihh, 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 of Dhh or Ihh, nor of the possible function of Shh during later embryogenesis. We have used serial-section in situ hybridization to obtain a detailed profile of mouse Hh gene expression from 11.5 to 16.5 days post coitum. Apart from the gut, which expresses both Shh and Ihh, there is no overlap in the various Hh expression domains. Shh is predominantly expressed in epithelia at numerous sites of epithelial-mesenchymal interactions, including the tooth, hair, whisker, rugae, gut, bladder, urethra, vas deferens, and lung, Dhh in Schwann and Sertoli cell precursors, and Ihh in gut and cartilage. Thus, it is likely that Hh signaling plays a central role in a diverse array of morphogenetic processes. Furthermore, we have compared Hh expression with that of a second family of signaling molecules, the Bone morphogenetic proteins (Bmps), vertebrate relatives of decapentaplegic, 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.

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

“…Third, overexpression of Cbfa1 in rib cartilage prematurely initiates Ihh transcription (Takeda et al, 2001;Ueta et al, 2001). Furthermore, Cbfa1 mRNA is up-regulated in prehypertrophic chondrocytes where Ihh expression is localized in the growth plate (Bitgood and McMahon, 1995;. It is conceivable, therefore, that Cbfa1 is upstream of Ihh and Cbfa1 may directly control Ihh expression in the growth plate.…”

“…Ihh is expressed in a narrow zone of prehypertrophic chondrocytes within growth plates and is an important regulator of growth plate activity (Bitgood and McMahon, 1995;Vortkamp et al, 1996;St-Jacques et al, 1999). To find out whether the expression of Ihh is affected in Grg5 null mice, Ihh expression was compared in Grg5 heterozygotes and growth-retarded Grg5 null mice by in situ hybridization.…”

Differential expression of fos and jun family members in the developing chicken gastrointestinal tract

“…Among them, we are especially interested in the Sonic hedgehog gene, because it has been reported to be involved in induction and patterning in mouse (Bitgood and McMahon, 1995) and chicken digestive tract (Roberts et al, 1995;Narita et al, 1998). Expression of Shh is known to start before tubular structure formation in epithelium of both foregut and hindgut (Roberts et al, 1995).…”

“…Shh functions as an endodermal signal which induces Ptc, Gli and Bmps in mesenchymal cells, and these genes form the inductive network between epithelium and mesenchyme of the digestive tract. Indian hedgehog (Ihh), another member of the hedgehog gene family, has also been reported to be expressed in mouse digestive tract in a unique manner that partly overlaps with to that of Shh (Bitgood and McMahon, 1995).…”

“…We have analysed the expression patterns of all the known chicken members of fos family genes (c-fos and fra-2) (Fujiwara et al, 1987;Nishina et al, 1990) and jun family genes (c-jun and junD) (Nishimura and Vogt 1988;Hartl et al, 1991) during gut development and compared them with those of the Sonic hedgehog (Shh) and Indian hedgehog (Ihh) genes reported to be involved in endodermal signaling and patterning in the gastrointestinal tract (Roberts et al, 1995;Bitgood and McMahon 1995).…”