Gli2 functions in FGF signaling during antero-posterior patterning.
Patterning along the anteroposterior (A-P) axis involves the interplay of secreted and transcription factors that specify cell fates in the mesoderm and neuroectoderm. While FGF and homeodomain proteins have been shown to play different roles in posterior specification, the network coordinating their effects remains elusive. Here we have analyzed the function of Gli zinc-finger proteins in mesodermal A-P patterning. We find that Gli2 is sufficient to induce ventroposterior development, functioning in the FGF-brachyury regulatory loop. Gli2 directly induces brachyury, a gene required and sufficient for mesodermal development, and Gli2 is in turn induced by FGF signaling. Moreover, the homeobox gene Xhox3, a critical determinant of posterior development, is also directly regulated by Gli2. Gli3, but not Gli1, has an activity similar to that of Gli2 and is expressed in ventroposterior mesoderm after Gli2. These findings uncover a novel function of Gli proteins, previously only known to mediate hedgehog signals, in the maintenance and patterning of the embryonic mesoderm. More generally, our results suggest a molecular basis for an integration of FGF and hedgehog inputs in Gli-expressing cells that respond to these signals.
Brewster
R
R
The Skirball Institute, Developmental Genetics Program and Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Mullor
J L
JL
Ruiz i Altaba
A
A
D000818:Animals; D000943:Antigens, Differentiation; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000378:metabolism; D004627:Embryonic Induction; D005326:Fetal Proteins; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D008648:Mesoderm; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000378:metabolism; D013623:Tail / Q000196:embryology; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D016335:Zinc Fingers; D000098908:Brachyury Protein
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011506:Proteins; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D000098908:Brachyury Protein; C094040:EVX1 protein, Xenopus; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; C400681:Hox3 protein, Ciona intestinalis