DLX GENES ENCODE DNA-BINDING PROTEINS THAT ARE EXPRESSED IN AN OVERLAPPING AND SEQUENTIAL PATTERN DURING BASAL GANGLIA DIFFERENTIATION

The Dlx gene family encodes homeodomain proteins that are required for forebrain and craniofacial development. Towards elucidating the roles for each of these genes, we have isolated cDNA clones encoding the fu ll-coding sequence for murine Dlx-5 and partial coding sequence For mu rine Dlx-6. Three different classes of sense Dlx-5 cDNA clones were ch aracterized, two of which lack. the homeobox. We also identified an an tisense Dlx-6 transcript. Genomic analysis shows that the Dlx-5 and -6 genes are linked. Biochemical analysis using gel shift assays demonst rate that DLX-1, -2 and -5 have very similar DNA-binding properties. T he expression of Dlx-1, -2, -5, -6 and antisense Dlx-1 and -6 was stud ied in the midgestation mouse brain. We found that the Dir genes are e xpressed in overlapping patterns at different stages of differentiatio n within the primordia of the basal ganglia. Dlx-1 and -2 are expresse d in the least mature cells (in the ventricular and subventricular zon es). Dlx-5 appears to be co-expressed with Dlx-1 and -2 in the SVZ, bu t is also expressed in the postmitotic cells of the mantle. Dlx-6 expr ession is strongest in the mantle. Antisense Dlx-1 and -6 have their h ighest expression in the SVZ. These results suggest that each of these Dir genes may have a distinct role in different steps of differentiat ion in the basal ganglia. (C) 1997 Wiley-Liss, Inc.