Tcf7l1 protects the anterior neural fold from adopting the neural crest fate.
The neural crest (NC) is crucial for the evolutionary diversification of vertebrates. NC cells are induced at the neural plate border by the coordinated action of several signaling pathways, including Wnt/β-catenin. NC cells are normally generated in the posterior neural plate border, whereas the anterior neural fold is devoid of NC cells. Using the mouse model, we show here that active repression of Wnt/β-catenin signaling is required for maintenance of neuroepithelial identity in the anterior neural fold and for inhibition of NC induction. Conditional inactivation of Tcf7l1, a transcriptional repressor of Wnt target genes, leads to aberrant activation of Wnt/β-catenin signaling in the anterior neuroectoderm and its conversion into NC. This reduces the developing prosencephalon without affecting the anterior-posterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient.
Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague 142 20, Czech Republic.
Jan
J
Mašek
Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague 142 20, Czech Republic machon@img.cas.cz.
Ondřej
0000-0002-5139-1406
O
Machoň
Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague 142 20, Czech Republic.
Vladimír
V
Kořínek
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
M Mark
MM
Taketo
Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague 142 20, Czech Republic.
Zbyněk
Z
Kozmik
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D017353:Gene Deletion; D006801:Humans; D019426:Integrases / Q000378:metabolism; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D009436:Neural Tube Defects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015415:Biomarkers; D012097:Repressor Proteins; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D050656:Transcription Factor AP-2; D029961:Zebrafish Proteins; D051176:beta Catenin; C544914:tcf7l1a protein, zebrafish; C045073:Cre recombinase; D019426:Integrases
Forebrain; Mouse; Neural crest; Tcf/Lef; Wnt signaling; Zebrafish