Lacking of palladin leads to multiple cellular events changes which contribute to NTD.
BACKGROUND
The actin cytoskeleton-associated protein palladin plays an important role in cell motility, morphogenesis and adhesion. In mice, Palladin deficient embryos are lethal before embryonic day (E) 15.5, and exhibit severe cranial neural tube and body wall closure defects. However, the mechanism how palladin regulates the process of cranial neural tube closure (NTC) remains unknown.


METHODS
In this paper, we use gene knockout mouse to elucidate the function of palladin in the regulation of NTC process.


RESULTS
We initially focuse on the expression pattern of palladin and found that in embryonic brain, palladin is predominantly expressed in the neural folds at E9.5. We further check the major cellular events in the neural epithelium that may contribute to NTC during the early embryogenesis. Palladin deficiency leads to a disturbance of cytoskeleton in the neural tube and the cultured neural progenitors. Furthermore, increased cell proliferation, decreased cell differentiation and diminished apical cell apoptosis of neural epithelium are found in palladin deficient embryos. Cell cycle of neural progenitors in Palladin-/-embryos is much shorter than that in wt ones. Cell adhesion shows a reduction in Palladin-/-neural tubes.


CONCLUSIONS
Palladin is expressed with proper spatio-temporal pattern in the neural folds. It plays a crucial role in regulating mouse cranial NTC by modulating cytoskeleton, proliferation, differentiation, apoptosis, and adhesion of neural epithelium. Our findings facilitate further study of the function of palladin and the underlying molecular mechanism involved in NTC.
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China.|Model Organism Division, E-Institutes of Shanghai Universities, SJTUSM, Shanghai, 200025, China.
Juan
J
Tan
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China.|Model Organism Division, E-Institutes of Shanghai Universities, SJTUSM, Shanghai, 200025, China.
Xue-Jiao
XJ
Chen
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China.
Chun-Ling
CL
Shen
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China.
Hong-Xin
HX
Zhang
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China.|Model Organism Division, E-Institutes of Shanghai Universities, SJTUSM, Shanghai, 200025, China.
Ling-Yun
LY
Tang
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China.
Shun-Yuan
SY
Lu
Shanghai Research Center for Model Organisms, Shanghai, 201203, China.
Wen-Ting
WT
Wu
Shanghai Research Center for Model Organisms, Shanghai, 201203, China.
Ying
Y
Kuang
Shanghai Research Center for Model Organisms, Shanghai, 201203, China.
Jian
J
Fei
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Building 17, No. 197, Ruijin 2nd Rd, Shanghai, 200025, China. zhugangw@shsmu.edu.cn.|Model Organism Division, E-Institutes of Shanghai Universities, SJTUSM, Shanghai, 200025, China. zhugangw@shsmu.edu.cn.|Shanghai Research Center for Model Organisms, Shanghai, 201203, China. zhugangw@shsmu.edu.cn.
Zhu-Gang
ZG
Wang
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000378:metabolism; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism*; D009436:Neural Tube Defects / Q000196:embryology* / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; C485873:palladin protein, mouse
Apoptosis; Cytoskeleton; Differentiation; Neural tube defect; Palladin; Proliferation