Fig. 3.

We show comparison of temporal patterns of terminal mitosis in the cochlea of the wild type and Neurog1 null littermates imaged at E18.5 (A, – C), and of Neurod1–LacZ expression at E18.5 in a Neurod1-LacZ heterozygote wild type and Neurog1 null littermate (D–G). In the absence of Neurog1, the hair cells exhibit alteration of the temporal pattern of terminal mitosis. BrdU injection at E9.5 and examination of the cochlea at E18.5 reveals some fully labeled nuclei (i.e. terminal mitotic cells) in the apex of the Neurog1 mutant cochlea (arrows in C; green is autofluorescence of hair cells). BrdU injected at E11.5 labels cells in the middle turn of the organ of Corti (OC) with only specks of BrdU labeling in wildtype (A) and shows prominent nuclear labeling of spiral ganglion neurons (Spgl in A). In Neurog1 null littermates there are no spiral ganglion cells (B). Instead, a prominent labeling of hair cell nuclei of the organ of Corti indicates a premature terminal mitosis of hair cells in the middle turn in a pattern similar to the proliferation of spiral ganglion neurons in wild-type (compare A, B). Similar effects on altered expression patterns are found in Neurod1 expression in Neurog1 null mutants and wildtype littermates (D–G). At E18.5, spiral neurons are strongly labeled for Neurod1 in the wild-type ear (D). In contrast to the very faint labeling of the wild-type organ of Corti, the Neurog1 null ear (E) shows profound Neurod1-LacZ staining in many hair cells. Note the absence of spiral ganglion neurons in Neurog1 null mice (compare D and E) and the multiple rows of outer hair cells (OHC) in the apex of the mutant cochlea (compare F and G). IHC, inner hair cell; OC, Organ of Corti; Spgl, spiral ganglion. Bar scale indicates 100 μm in A, B, D, E and 10μm in C, F, G.