Abstract
The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.
Highlights
Neural crest cells (NCCs) are a transient and multipotent cell population unique to vertebrates
We show that the facial clefting phenotype of PDGFRa mutants is not associated with a defect in neural crest cell specification but rather a subsequent defect in the medial nasal process (MNP), a facial primordium derived from the frontonasal prominence
We further show that this defect is associated with alterations in both cell proliferation and cell migration, and that PI3K and Rac1 signaling are essential to maintain a normal level of cell proliferation
Summary
Neural crest cells (NCCs) are a transient and multipotent cell population unique to vertebrates. At the onset of craniofacial development, the facial primordium is composed of five prominences surrounding the stomodeum: the frontonasal prominence (FNP) at the rostral region, two paired maxillary processes in the middle, and a pair of mandibular processes at the caudal end [6,7] These primordia are populated predominantly by NCC derived cells, surrounding a mesodermal core and covered by the overlying ectoderm. Vital dye labeling studies reveal that the NCCs giving rise to different facial prominences share distinct origins along the rostralcaudal axis: NCCs from the diencephalon and anterior mesencephalon give rise to the MNP and LNP, while those originating from the posterior mesencephalon and hindbrain give rise to the maxilla and mandible [10,11] These results suggest that the MNP and other prominences may be regulated through different mechanisms
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