Pdgfra and Pdgfrb Genetically Interact in the Murine Neural Crest Cell Lineage to Regulate Migration and Proliferation.
Pdgfra and Pdgfrb Genetically Interact in the Murine Neural Crest Cell Lineage to Regulate Migration and Proliferation.
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DOI：
10.3389/fphys.2020.588901
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发表时间：
2020
影响因子：
4
通讯作者：
Fantauzzo KA
中科院分区：
文献类型：
--
作者：
Mo J;Long R;Fantauzzo KA
颅神经嵴细胞（cNCC）是一种可迁移的多能细胞，起源于前脑到后脑，最终产生额鼻骨架的软骨和骨，以及其他衍生物。通过受体酪氨酸激酶的血小板衍生生长因子受体（PDGFR）家族的两个成员α和β的信号传导在cNCC谱系中起关键作用，以调节鼠胚胎发生期间的颅面发育。此外，PDGFR已被证明在妊娠中期至晚期的小鼠颅面发育期间遗传相互作用。在这里，我们研究了在小鼠NCC谱系中消融Pdgfra和Pdgfrb对早期颅面发育的影响，并确定了所观察到的表型出现的细胞机制。我们的研究结果证实了这两个受体在这一谱系中的遗传相互作用，因为在突变胚胎的等位基因系列中观察到的表型往往随着条件等位基因的加入而恶化。此处观察到的缺陷似乎源于异常cNCC迁移，以及PDGFRα和PDGFRβ信号传导联合降低后面部间充质增殖降低。重要的是，我们发现PDGFRα在cNCC迁移中起主要作用，而PDGFRβ主要促进妊娠中期后面部间充质的增殖。我们的研究结果提供了对PDGFRα和PDGFRβ信号调节小鼠胚胎cNCC活性和随后颅面发育的不同机制的深入了解。
Cranial neural crest cells (cNCCs) are migratory, multipotent cells that originate from the forebrain to the hindbrain and eventually give rise to the cartilage and bone of the frontonasal skeleton, among other derivatives. Signaling through the two members of the platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases, alpha and beta, plays critical roles in the cNCC lineage to regulate craniofacial development during murine embryogenesis. Further, the PDGFRs have been shown to genetically interact during murine craniofacial development at mid-to-late gestation. Here, we examined the effect of ablating both Pdgfra and Pdgfrb in the murine NCC lineage on earlier craniofacial development and determined the cellular mechanisms by which the observed phenotypes arose. Our results confirm a genetic interaction between the two receptors in this lineage, as phenotypes observed in an allelic series of mutant embryos often worsened with the addition of conditional alleles. The defects observed here appear to stem from aberrant cNCC migration, as well as decreased proliferation of the facial mesenchyme upon combined decreases in PDGFRα and PDGFRβ signaling. Importantly, we found that PDGFRα plays a predominant role in cNCC migration whereas PDGFRβ primarily contributes to proliferation of the facial mesenchyme past mid-gestation. Our findings provide insight into the distinct mechanisms by which PDGFRα and PDGFRβ signaling regulate cNCC activity and subsequent craniofacial development in the mouse embryo.
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