Redundant type II cadherins define neuroepithelial cell states for cytoarchitectonic robustness

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 mice develop intermingled forebrain/midbrain compartments as these two cadherins' expression opposes at the nascent boundary. Cdh6/8/11 triple, Cdh6/8 double or Cdh8/11 double knockout mice further cause exencephaly just within the cranial region where mutated cadherins' expression merges. In the Cdh8/11 double knockout 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. Overall design: The mRNA profiles of the forebrain and midbrain tissues from type II cadherin double and triple knockout mice (E9.5) were generated using the Illumina HiSeq platforms. The numbers of each replicate are three to six, and the total number of samples is 32.