Shh/BMP-4 signaling pathway is essential for intestinal epithelial development during Xenopus larval-to-adult remodeling.
During amphibian larval-to-adult intestinal remodeling, progenitor cells of the adult epithelium actively proliferate and differentiate under the control of thyroid hormone (TH) to form the intestinal absorptive epithelium, which is analogous to the mammalian counterpart. We previously found that TH-up-regulated expression of bone morphogenetic protein-4 (BMP-4) spatiotemporally correlates with adult epithelial development in the Xenopus laevis intestine. Here, we aimed to clarify the role of BMP-4 in intestinal remodeling. Our reverse transcriptase-polymerase chain reaction and in situ hybridization analyses indicated that mRNA of BMPR-IA, a type I receptor of BMP-4, is expressed in both the developing connective tissue and progenitor cells of the adult epithelium. More importantly, using organ culture and immunohistochemical procedures, we have shown that BMP-4 not only represses cell proliferation of the connective tissue but promotes differentiation of the intestinal absorptive epithelium. In addition, we found that the connective tissue-specific expression of BMP-4 mRNA is up-regulated by sonic hedgehog (Shh), whose epithelium-specific expression is directly induced by TH. These results strongly suggest that the Shh/BMP-4 signaling pathway plays key roles in the amphibian intestinal remodeling through epithelial-connective tissue interactions.
Ishizuya-Oka
Atsuko
A
Department of Biology, Nippon Medical School, Kawasaki, Kanagawa, Japan. a-oka@nms.ac.jp
Hasebe
Takashi
T
Shimizu
Katsuhiko
K
Suzuki
Kenichi
K
Ueda
Shuichi
S
D000818:Animals; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D049109:Cell Proliferation; D003238:Connective Tissue / Q000254:growth & development / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008954:Models, Biological; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000378:metabolism; D015854:Up-Regulation; D029867:Xenopus Proteins / Q000235:genetics*; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D013963:Thyroid Hormones; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C054234:chordin; D052005:Bone Morphogenetic Protein Receptors, Type I