Shh and Wnt signaling pathways converge to control Gli gene activation in avian somites.
The regulation of the Gli genes during somite formation has been investigated in quail embryos. The Gli genes are a family encoding three related zinc finger transcription factors, Gli1, Gli2 and Gli3, which are effectors of Shh signaling in responding cells. A quail Gli3 cDNA has been cloned and its expression compared with Gli1 and Gli2. These studies show that Gli1, Gli2 and Gli3 are co-activated at the time of somite formation, thus providing a mechanism for regulating the initiation of Shh signaling in somites. Embryo surgery and paraxial mesoderm explant experiments show that each of the Gli genes is regulated by distinct signaling mechanisms. Gli1 is activated in response to Shh produced by the notochord, which also controls the dorsalization of Gli2 and Gli3 following their activation by Wnt signaling from the surface ectoderm and neural tube. This surface ectoderm/neural tube Wnt signaling has both negative and positive functions in Gli2 and Gli3 regulation: these signals repress Gli3 in segmental plate mesoderm prior to somite formation and then promote somite formation and the somite-specific activation of Gli2 and Gli3. These studies, therefore, establish a role for Wnt signaling in the control of Shh signal transduction through the regulation of Gli2 and Gli3, and provide a mechanistic basis for the known synergistic actions of surface ectoderm/neural tube and notochord signaling in somite cell specification.
Borycki
A
A
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, BRBII/III, Philadelphia, PA 19104-6058, USA.
Brown
A M
AM
Emerson
C P
CP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics*; D004475:Ectoderm; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009672:Notochord; D015513:Oncogene Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011784:Quail / Q000196:embryology; D051381:Rats; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D019170:Somites; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D051153:Wnt Proteins; D060528:Wnt4 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3; D016335:Zinc Fingers; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555584:Wnt4 protein, Xenopus; C555582:Wnt4 protein, mouse; C555583:Wnt4 protein, rat; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3; D051176:beta Catenin