Abstract
Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.
Highlights
A unique feature of vertebrate neurulation is the delamination of neural crest progenitors from the dorsal neuroepithelium before and during neural tube formation
Since Pdgfrß+ mesenchymal cells reach their highest density in the dorsomedial region of the midline mesenchyme, apposed to the cortical hem, a source of Wnt secretion, we examined whether the cells were responding to Wnt signaling at this stage
Our findings suggest that ß-catenin signaling of interhemispheric mesenchymal cells is required for the development and invagination of the dorsal telencephalic midline, and formation of the lateral ventricles. We examined both loss and gain of function mutations of ß-catenin signaling in rostral neural crest-derived cells and showed that ß-catenin signaling is important for the initial expansion of mesenchymal stem cells (MSCs) in the dorsal interhemispheric region and the invagination of the dorsal telencephalic region
Summary
A unique feature of vertebrate neurulation is the delamination of neural crest progenitors from the dorsal neuroepithelium before and during neural tube formation. We hypothesized that Wnts secreted from the cortical hem act as a proliferative signal on neural crest derived mesenchymal progenitor cells, which induces their expansion adjacent to the dorsomedial telencephalon and that this initial expansion of mesenchymal progenitor cells contributes to neural crest derived craniofacial structures and proper development of the forebrain. To address this question, we conditionally manipulated ß-catenin in late premigratory neural crest cells using Sox10-Cre mice [29]. Our results clearly demonstrate that Wnt/ß-catenin signaling plays a critical role in the development of neural crest-derived mesenchymal derivatives and that dorsomedial mesenchymal progenitors contribute to cortical midline invagination and lateral ventricle formation
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