BMP signaling in the development of the mouse esophagus and forestomach.
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The stratification and differentiation of the epidermis are known to involve the precise control of multiple signaling pathways. By contrast, little is known about the development of the mouse esophagus and forestomach, which are composed of a stratified squamous epithelium. Based on prior work in the skin, we hypothesized that bone morphogenetic protein (BMP) signaling is a central player. To test this hypothesis, we first used a BMP reporter mouse line harboring a BRE-lacZ allele, along with in situ hybridization to localize transcripts for BMP signaling components, including various antagonists. We then exploited a Shh-Cre allele that drives recombination in the embryonic foregut epithelium to generate gain- or loss-of-function models for the Bmpr1a (Alk3) receptor. In gain-of-function (Shh-Cre;Rosa26(CAG-loxpstoploxp-caBmprIa)) embryos, high levels of ectopic BMP signaling stall the transition from simple columnar to multilayered undifferentiated epithelium in the esophagus and forestomach. In loss-of-function experiments, conditional deletion of the BMP receptor in Shh-Cre;Bmpr1a(flox/flox) embryos allows the formation of a multilayered squamous epithelium but this fails to differentiate, as shown by the absence of expression of the suprabasal markers loricrin and involucrin. Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach.
Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein Receptors, Type I
Bone Morphogenetic Proteins
Gene Expression Regulation, Developmental
In Situ Hybridization
Published Version (Please cite this version)10.1242/dev.056077
Publication InfoRodriguez, Pavel; Da Silva, Susana; Oxburgh, Leif; Wang, Fan; Hogan, Brigid LM; & Que, Jianwen (2010). BMP signaling in the development of the mouse esophagus and forestomach. Development, 137(24). pp. 4171-4176. 10.1242/dev.056077. Retrieved from https://hdl.handle.net/10161/4178.
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George Barth Geller Distinguished Professor for Research in Molecular Biology
1. Genetic regulation of embryo development using the mouse as a research model. 2. The role of genes and signaling pathways in directing and co-ordinating the development of the lung. 3. The identity and regulation of the different stem cells in the adult lung and their role in repair, fibrosis and cancer.
Morris N. Broad Distinguished Professor
My lab studies neural circuit basis of sensory perception. Specifically we are interested in determining neural circuits underlying (1) active touch sensation including tactile processing stream and motor control of touch sensors on the face; (2) pain sensation including both sensory-discriminative and affective aspects of pain; and (3) general anesthesia including the active pain-suppression process. We use a combination of genetic, viral, electrophysiology, and in vivo imaging (in f
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