TY - JOUR
T1 - Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities
AU - Panoutsopoulos, Alexios A.
AU - De Crescenzo, Angelo Harlan
AU - Lee, Albert
AU - Lu, Amelia Mac Kenzie
AU - Ross, Adam P.
AU - Borodinsky, Laura N.
AU - Marcucio, Ralph
AU - Trainor, Paul A.
AU - Zarbalis, Konstantinos S.
N1 - Funding Information:
We thank Kirsten Lois Ner and Michael Podesta, for technical assistance. We also thank Dr. Athena Soulika for advice and support with flow cytometry. Funding. This study was supported by Shriners Hospitals for Children and NIH grant R01DE022830 to KZ, PT, and RM. Research in the Trainor laboratory is supported by the Stowers Institute for Medical Research.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - development
KW - mouse
KW - neural crest
KW - orofacial clefts
KW - Pak1ip1
KW - ribosomopathies
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U2 - 10.3389/fcell.2020.510063
DO - 10.3389/fcell.2020.510063
M3 - Article
AN - SCOPUS:85090961654
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
SN - 2296-634X
M1 - 510063
ER -