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Fig. 11. Premature loss of neuroepithelial and radial glial cells in Hes1;Hes3;Hes5 triple mutants. (A-D) At E8.0, like Hes1 (A), Hes3 is expressed in the nervous system (B) whereas Hes5 and Dll1 are not (C,D). (E-H) At E8.5, while Hes1 is still diffusely expressed (E), Hes3 expression domain is restricted to the medial to dorsal region (F). Hes5 and Dll1 expression is observed at this stage (G,H). (I,J) Hes3 is widely expressed in the developing nervous system at E8.0 (I) and E8.5 (J). The head region is indicated by arrowheads. (K-M) Hes3 expression is not significantly affected in the Hes1;Hes5 double mutant, compared with the wild type. (N-R) At E8.5, very few neurons (TuJ1⁺) are generated in both the wild type and Hes1;Hes5 double mutant (N,O) whereas in Hes1;Hes3;Hes5 triple-mutant, many neurons are prematurely differentiated (P). There are still many neuroepithelial cells (nestin⁺Ki67⁺) in the Hes1;Hes5 double mutant (Q,R). (S) At E9.5, more neurons are prematurely differentiated in the ventral region of Hes1;Hes3;Hes5 triple-mutant spinal cord. (T-V) At E10.0, the structure of the spinal cord is severely disorganized in Hes1;Hes3;Hes5 triple mutants (T). Strikingly, virtually all cells become neurons (U), and radial glia are missing (V). Scale bars: 100 µm in A-H,N-V.

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