1. Redundant type II cadherins define neuroepithelial cell states for cytoarchitectonic robustness
- Author
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Mikio Hoshino, Kou Hiraga, Takayoshi Inoue, Yukiko U. Inoue, Junko Asami, Shoji Tatsumoto, Yasuhiro Go, Yuki Morimoto, and Mayuko Hotta
- Subjects
Embryology ,Neural Tube ,Morphogenesis ,Neuroepithelial Cells ,Medicine (miscellaneous) ,Embryonic Development ,Fluorescent Antibody Technique ,Biology ,Exencephaly ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Animals ,Humans ,lcsh:QH301-705.5 ,Actin ,030304 developmental biology ,Gene Editing ,0303 health sciences ,Neural Plate ,Cadherin ,Chromosome Mapping ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Genomics ,medicine.disease ,Cadherins ,Immunohistochemistry ,Cell biology ,Neuroepithelial cell ,Neurulation ,lcsh:Biology (General) ,Forebrain ,Gene Targeting ,CRISPR-Cas Systems ,General Agricultural and Biological Sciences ,Neural plate ,030217 neurology & neurosurgery - Abstract
Individual cell shape and integrity must precisely be orchestrated during morphogenesis. Here, we determine function of type II cadherins, Cdh6, Cdh8, and Cdh11, whose expression combinatorially demarcates the mouse neural plate/tube. While CRISPR/Cas9-based single type II cadherin mutants show no obvious phenotype, Cdh6/8 double knockout (DKO) mice develop intermingled forebrain/midbrain compartments as these two cadherins’ expression opposes at the nascent boundary. Cdh6/8/11 triple, Cdh6/8 or Cdh8/11 DKO mice further cause exencephaly just within the cranial region where mutated cadherins’ expression merges. In the Cdh8/11 DKO midbrain, we observe less-constricted apical actin meshwork, ventrally-directed spreading, and occasional hyperproliferation among dorsal neuroepithelial cells as origins for exencephaly. These results provide rigid evidence that, by conferring distinct adhesive codes to each cell, redundant type II cadherins serve essential and shared roles in compartmentalization and neurulation, both of which proceed under the robust control of the number, positioning, constriction, and fluidity of neuroepithelial cells., Hiraga et al. generate knockout mice lacking type II cadherins Cdh6, Cdh8 and Cdh11 to elucidate their role in the developing CNS. Whereas no phenotype is observed in single knockouts, the analysis of double and triple knockouts show that type II cadherins serve essential and shared roles in compartmentalization and neurulation.
- Published
- 2020