Disruption of palladin results in neural tube closure defects in mice.
Palladin is a newly identified actin-associated protein which was proposed to be involved in actin cytoskeleton organization and nervous system development. Here, we show that inactivation of palladin leads to embryonic lethality due to severe defects of cranial neural tube closure and herniation of liver and intestine. It was found that palladin(-/-) embryos died around E15.5 and developed cranial neural tube closure defects (NTDs) with 100% penetrance. Whole mount in situ hybridization revealed that expression of palladin in early wild type embryos (E8.5) was specifically restricted in the elevating cranial neural folds where the neural tube closure is initiated. Palladin expression closely mirrors the phenotypic defects observed in palladin(-/-) mutants. While in E 9.5 and E10.5 embryos palladin was ubiquitously expressed. In vitro study revealed that formation of stress fibers in cytoplasm, cell adherent ability to extra-cellular matrix protein fibronectin and cell migration were dramatically disturbed in palladin(-/-) murine embryonic fibroblast cells (MEFs). Our findings suggest that palladin plays important roles in actin stress fiber formation, cell adhesion and migration. We propose that palladin is required for the initiation of neural tube closure and provides an important new candidate that may be implicated in the etiology of human NTDs.
Luo
Huijun
H
Laboratory of Genetic Engineering, Department of Medical Genetics, Institute of Health Science, Shanghai Second Medical University, 280 South Chong-qing Road, Shanghai 200025, PR China.
Liu
Xuesong
X
Wang
Fang
F
Huang
Qiuhua
Q
Shen
Shuhong
S
Wang
Long
L
Xu
Guojiang
G
Sun
Xia
X
Kong
Hui
H
Gu
Mingmin
M
Chen
Saijuan
S
Chen
Zhu
Z
Wang
Zhugang
Z
D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002678:Chimera; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000235:genetics; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D010750:Phosphoproteins / Q000235:genetics*; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D003598:Cytoskeletal Proteins; D005353:Fibronectins; D010750:Phosphoproteins; C485873:palladin protein, mouse