DLX-2 HOMEOBOX GENE CONTROLS NEURONAL DIFFERENTIATION IN PRIMARY CULTURES OF DEVELOPING BASAL GANGLIA

Homeodomain-containing genes of the Dlx family are expressed in the de veloping basal ganglia. To investigate the role of Dlx genes during de velopment, we studied their cellular localization in primary cultures of embryonic basal telencephalon, and examined the changes in cellular phenotypes resulting from blockade of Dlx-2 expression. Cells contain ing Dlx-1, Dlx-2, and Dlx-5 mRNAs are immature cells of the neuronal l ineage expressing the microtubule-associated proteins (MAPs) MAP1B and MAP2, but not glial fibrillary acidic protein (GFAP). Treatment of th ese cells with antisense oligonucleotides targeted to Dlx-2 caused a s pecific decrease of Dlx-2 mRNA and protein. This decrease in the Dlx-2 gene product was associated with a decrease in the expression of MAP2 , a protein localized in neuronal dendrites, along with a smaller decr ease in the 200-kDa neurofilament subunit (NF-H). Proteins expressed p referentially in axons were unchanged. This reduction in MAP2 expressi on was associated with a decrease in dendrite outgrowth and an increas ed level of cell proliferation. None of these changes were elicited by antisense oligonucleotides targeted to Dlx-1. We suggest that the Dlx -2 gene product regulates two interrelated aspects of neuronal differe ntiation: the exit from the mitotic cycle and the capability to grow M AP2-positive dendrites. As such, this gene product may be important fo r the establishment of neuronal polarity, setting the stage for affere nt synaptic connectivity.