Tcf7l1 protects the anterior neural fold from adopting the neural crest fate

Abstract

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 anteriorposterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient.

β-catenin and γ-catenin are dispensable for T lymphocytes and AML leukemic stem cells

“…While ablation of Tcf4 protein was also effective in thymocytes as determined by immunoblotting ( Figure 4B ), Tcf3 protein was not reliably detected in thymocytes or BM cells (not shown), likely due to its expression in very low abundance (see Figure 4C ). It should be noted that deletion efficacy for Tcf3 protein was independently verified in mouse embryonic fibroblasts in a recent report using the same ES clone ( Mašek et al, 2016 ). We further verified with quantitative RT-PCR that the targeted exon in Tcf7l1 transcripts was as effectively deleted as that in Tcf7l2 transcripts, in spite of the low abundance ( Figure 4C ).…”

Tcf7L2 is essential for neurogenesis in the developing mouse neocortex

“…To test this assumption we employed tissue-specific deletion of these Tcf factors. We crossed forebrain-specific Cre driver mouse line D6-Cre allowing loxP-recombination in the neocortex from E11.5 [ 22 ] with conditional alleles of Tcf7L1 [ 23 ] and Tcf7L2 . D6-Cre/ROSA26 lineage tracing in whole-mounts and on coronal sections of brains at E13.5, E15.5 and newborns (P0) illustrated Cre activity in the lateral and medial neocortex (Cx) and in the hippocampus (Hi) (Fig.…”

“…Generation and description of these mouse strains has been described previously: D6-Cre [ 22 ], Tcf7L1 fl/fl [ 23 ], ROSA26 [ 34 ]. Tcf7L2 fl/fl mouse strain was generated from Tcf7l2 tm1a(EUCOMM)Wtsi mice that were purchased from the European Conditional Mouse Mutagenesis Program EUCOMM (Welcome Trust Sanger Institute).…”

Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies

“…Unlike the rest of the vertebrate neural tube, the anterior forebrain neural folds do not generate neural crest cells, and the neural crest cells of the forebrain mesenchyme migrate in from the caudal forebrain and the midbrain [ 60 , 94 , 95 , 96 ]. In mouse embryos, the transcription factor Tcf7l1 expressed in the anterior forebrain neural folds acts to repress the Wnt/B-catenin pathway that otherwise would induce neuroectoderm cells to become neural crest cells [ 97 ]. Loss of Tcf7l1 leads to conversion of the neuroectoderm of the most rostral neural folds to neural crest cells and a subsequent reduction of the rostral forebrain, which if severe is accompanied by exencephaly [ 97 ].…”

“…In mouse embryos, the transcription factor Tcf7l1 expressed in the anterior forebrain neural folds acts to repress the Wnt/B-catenin pathway that otherwise would induce neuroectoderm cells to become neural crest cells [ 97 ]. Loss of Tcf7l1 leads to conversion of the neuroectoderm of the most rostral neural folds to neural crest cells and a subsequent reduction of the rostral forebrain, which if severe is accompanied by exencephaly [ 97 ]. Interestingly, in the images published, the midbrain also appears to be reduced.…”