Fig. 8: Dorsal neuroepithelial cells spread ventrally in the Cdh8/11 DKO Mb.

a E9.0 embryos are sectioned at anterior and posterior levels (AL and PL) in c, e, g and i. b Definition of relative positions in the neural plate/tube (RPN) is outlined. The length of the ventricular surface from the tip of the neural fold to the ventral hinge point (=L) is equally divided into eight portions (=L/8). By setting tangential lines at the divided points and drawing vertical lines to the tangents towards the mantle zone, the neural fold is partitioned into eight areas (1~8). c, e, g, and i, ISH for mRNA for the D-V patterning molecules is performed in WT and Cdh8/11 DKO mice. Scale bar: 100 μm. d, f, h, and j Mean occupancy of mRNA-positive cells across the neural plate/tube, derived from images including c, e, g, and i, is graphed along the eight areas. Gray and pink lines indicate individual data in WT and Cdh8/11 DKO, respectively. Bold black and red lines show means for WT and Cdh8/11 DKO mice. Note that the signal distribution patterns in the Cdh8/11 DKO mice (red line) are shifted to the ventral side compared with those in WT (black line). k Diagram shows patterns of cranial neural tube closure in WT or multiple Cdh KO embryos in the transverse view at the Mb. t, time in development; TKO, triple KO. Cells with dorsally expressed genes like Cdh6 (purple) are restricted in their movement in WT. If neuroepithelial cells, normally expressing redundant Cdhs, lose their original adhesive code, the cellular fluidity increases (Cdh DKO or TKO). Cells with less capacity for actin meshwork contractility could drift ventrally as clusters from the original position and disrupt the critical population of cells like those at the dorsolateral hinge point (DLHP) to prevent bending of the neural plate. Increased proliferation of those cells might enhance the probability for the DLHP disruptions, finally resulting in exencephaly.