Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities
Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities
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DOI：
10.3389/fcell.2020.510063
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发表时间：
2020-09
影响因子：
5.5
通讯作者：
A. Panoutsopoulos;Angelo Harlan De Crescenzo;Albert Lee;A. M. Lu;A. Ross;L. N. Borodinsky;R. Marcucio;P. Trainor;K. Zarbalis
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文献类型：
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作者：
A. Panoutsopoulos;Angelo Harlan De Crescenzo;Albert Lee;A. M. Lu;A. Ross;L. N. Borodinsky;R. Marcucio;P. Trainor;K. Zarbalis
神经嵴细胞（NCC）包括神经上皮来源的瞬时祖细胞群体，其在整个脊椎动物胚胎中贡献多种细胞类型，包括颅和面部结构的大多数间充质细胞。因此，NCC发育异常是各种颅面缺陷的基础，包括口面裂，口面裂构成了一些最常见的出生缺陷。我们以前报道的一代曼塔射线（mray）小鼠携带的基因编码的前核糖体因子Pak1ip 1的功能丧失的等位基因。在这里，我们描述了纯合子mray突变体的颅骨骼异常，所产生的NCC后，他们的规范的损失。我们的研究结果表明，在发展中的额鼻咽喉的局部损失的颅NCCs是由细胞周期停滞和细胞死亡。此外，与核糖体生物合成缺陷一致，纯合mray突变体显示蛋白质生物合成减少，进一步将Pak1ip1与核糖体生物合成中的作用联系起来。
Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a variety of craniofacial defects including orofacial clefts, which constitute some of the most common birth defects. We previously reported the generation of manta ray (mray) mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1. Here we describe cranioskeletal abnormalities in homozygous mray mutants that arise from a loss of NCCs after their specification. Our results show that the localized loss of cranial NCCs in the developing frontonasal prominences is caused by cell cycle arrest and cell death. In addition, and consistent with deficits in ribosome biosynthesis, homozygous mray mutants display decreased protein biosynthesis, further linking Pak1ip1 to a role in ribosome biogenesis.