Basic—Alimentary TractParacrine Hedgehog Signaling in Stomach and Intestine: New Roles for Hedgehog in Gastrointestinal Patterning
Section snippets
Mice
Gli1+/LacZ, Gli2+/LacZ, and Ptch1+/LacZ mice have been described.20, 27, 28, 29 Shh+/LacZ mice were used in a previous study30; their derivation will be described elsewhere (Gonzalez and Kottman, manuscript in preparation). Heterozygous mice were mated with C57Bl/6 mice, and the morning of vaginal plug was counted as embryonic day (E) 0.5. Genotyping was performed as previously described.20, 27, 28, 29, 30 Protocols for X-gal staining, immunostaining, in situ hybridization, quantitative
Results
Although Gli1, Gli2, and Ptch1 are all components of the Hh pathway, they reveal different aspects of the Hh signaling network. Gli1 is a direct target of Hh, and its expression is dependent on active Hh signaling.27 Ptch1 is also an Hh target gene, but its transcription is not solely dependent on Hh. Finally, Gli2 is an important mediator of activation,27 but its expression is not transcriptionally regulated by Hh. Thus, Ptch1LacZ/+ and Gli2LacZ/+ mice indicate cells capable of responding to
Discussion
This analysis of Hh signal response in the developing and mature gastrointestinal tract provides a cellular basis for Hh function in this tissue and suggests new avenues for exploration. Novel findings include the following: (1) shortly after gut tube formation, epithelial cells of the hindgut and tailgut express Ptch1 but not Gli1; (2) serosal cells respond to Hh signals during fetal life; (3) the developing MM contains Hh-responsive cells at P10 and continues to receive Hh signals during
Acknowledgments
Å.K.'s current address is: Karolinska Institutet, Department of Biosciences and Nutrition, Novum, SE-141 57 Huddinge, Sweden.
The authors thank the Organogenesis Morphology Core and the Microscopy and Image Analysis Laboratory for excellent technical support.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by National Institutes of Health grants R01 DK065850 (to D.L.G.) and P01 DK62041 (to D.L.G., J.L.M., and A.A.D.); the Organogenesis Training Program, T32-HD007505 (to W.J.Z., A.S.G., and Å.K.); and the Hematology Training Program, T32-HL07622 (to K.D.W.).