Fig. 5: Multiple loss of type II Cdh genes results in the cranial neural tube defect.

a Multiple elimination of type II Cdh genes causes exencephaly at E12.5. Notably, exencephaly occurs just within the cranial region where mutated type II Cdh expression merges (Fig. 2x). Scale bar: 2 mm. b Occurrence of exencephaly under the B6C3 hybrid background is summarized in the table. Note that the more we delete type II Cdh genes (=number of red—in the table), the higher is the penetrance of exencephaly. c A section level for d–i in an E9.5 embryo is depicted. d–i Phalloidin and DAPI are used to visualize F-actin and cell nuclei, respectively, at the semi-coronal section of E9.5 embryos. f, i Enlarged views of the ventricular surface demarcated by the white frame f, i in the upper e, h are arranged. In contrast to the tight accumulation of F-actin in the WT ventricular surface f, phalloidin staining becomes weaker and discontinuous (white arrowhead) in Cdh8/11 DKO mice i. Scale bar: 100 μm. j, n Section level for k–l and o–q in an E9.0 or E9.5 embryo is depicted. k–m, o–q Neuroepithelial cells at E9.0 or E9.5 are immunostained with a dividing cell marker phosphorylated histone H3 (p-H3: green), Pax7 (magenta) and DAPI (blue) in the WT or Cdh8/11 DKO Mb. Scale bar: 100 μm. r Graph shows the average number of p-H3-positive cells in WT and Cdh8/11 DKO Mb. Blue bars, number of cells in the ventral domain; orange bars, number of cells in the dorsal domain defined by Pax7-stained area in panels m, q. All data points are shown along with the mean ± s.d. **P < 0.01; NS, non-significant. Note that excess proliferation of neuroepithelial cells is much confined within the dorsal domain at E9.5.