title: Disruption of palladin results in neural tube closure defects in mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Huijun
authors.initials: H
authors.lastname: Luo
authors.forename: Xuesong
authors.initials: X
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Huang
authors.forename: Shuhong
authors.initials: S
authors.lastname: Shen
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Guojiang
authors.initials: G
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.forename: Mingmin
authors.initials: M
authors.lastname: Gu
authors.forename: Saijuan
authors.initials: S
authors.lastname: Chen
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
mesh_terms: 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
chemical_list: D003598:Cytoskeletal Proteins; D005353:Fibronectins; D010750:Phosphoproteins; C485873:palladin protein, mouse