The homeobox genes in the Dlx family are required for differentiation of ba
sal forebrain neurons and craniofacial morphogenesis. Herein, we studied th
e expression of Dlx-1, Dlx-2, and Dlx-5 RNA and protein in the mouse forebr
ain from embryonic day 10.5 (E10.5) to E12.5. We provide evidence that Dlx-
2 is expressed before Dlx-1, which is expressed before Dlx-5. We also demon
strate that these genes are expressed in the same cells, which may explain
why single mutants of the DL genes have mild phenotypes. The DLX proteins a
re localized primarily to the nucleus, although DLX-5 also can be found in
the cytoplasm. During development, the fraction of Dir-positive cells incre
ases in the ventricular zone. Analysis of the distribution of DLX-1 and DLX
-2 in M-phase cells suggests that these proteins are distributed symmetrica
lly to daughter cells during mitosis. We propose that DLX-negative cells in
the ventricular zone are specified progressively to become DLX-2-expressin
g cells during neurogenesis; as these cells differentiate, they go on to ex
press DLX-1, DLX-5, and DLX-6. This process appears to be largely the same
in all regions of the forebrain that express the DL genes. In the basal tel
encephalon, these DLX-positive cells differentiate into projection neurons
of the striatum and pallidum as well as interneurons, some of which migrate
to the cerebral cortex and the olfactory bulb. (C) 1999 Wiley-Liss, Inc.