Mutual genetic antagonism involving GLI3 and dHAND prepatterns the vertebrate limb bud mesenchyme prior to SHH signaling.
The bHLH transcription factor dHAND is required for establishment of SHH signaling by the limb bud organizer in posterior mesenchyme, a step crucial to development of vertebrate paired appendages. We show that the transcriptional repressor GLI3 restricts dHAND expression to posterior mesenchyme prior to activation of SHH signaling in mouse limb buds. dHAND, in turn, excludes anterior genes such as Gli3 and Alx4 from posterior mesenchyme. Furthermore, genetic interaction of GLI3 and dHAND directs establishment of the SHH/FGF signaling feedback loop by restricting the BMP antagonist GREMLIN posteriorly. These interactions polarize the nascent limb bud mesenchyme prior to SHH signaling.
te Welscher
Pascal
P
Department of Developmental Biology, Faculty of Biology, Utrecht University, 3584CH Utrecht, The Netherlands.
Fernandez-Teran
Marian
M
Ros
Marian A
MA
Zeller
Rolf
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005121:Extremities / Q000196:embryology*; D005246:Feedback; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins; D018257:Helix-Loop-Helix Motifs; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D008648:Mesoderm / Q000648:ultrastructure*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014714:Vertebrates / Q000196:embryology*; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000074290:Zinc Finger Protein Gli3; D016335:Zinc Fingers
D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011506:Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000074290:Zinc Finger Protein Gli3; C416676:ALX4 protein, human; C113178:Grem1 protein, mouse; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C486400:GREM1 protein, Xenopus; C486399:GREM1 protein, human; C465571:Gli3 protein, mouse; C498766:Hand2 protein, mouse; C509239:SHH protein, human; C410915:hand2 protein, zebrafish