AUTHOR=Panoutsopoulos Alexios A. , De Crescenzo Angelo Harlan , Lee Albert , Lu Amelia MacKenzie , Ross Adam P. , Borodinsky Laura N. , Marcucio Ralph , Trainor Paul A. , Zarbalis Konstantinos S. 

TITLE=Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.510063

DOI=10.3389/fcell.2020.510063

ISSN=2296-634X

ABSTRACT=<p>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 <italic>manta ray</italic> (<italic>mray</italic>) mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1. Here we describe cranioskeletal abnormalities in homozygous <italic>mray</italic> 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 <italic>mray</italic> mutants display decreased protein biosynthesis, further linking Pak1ip1 to a role in ribosome biogenesis.</p>