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Dlx-2 homeobox gene controls neuronal differentiation in primary cultures of developing basal ganglia

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Abstract

Homeodomain-containing genes of theDlx family are expressed in the developing basal ganglia. To investigate the role ofDlx genes during development, we studied their cellular localization in primary cultures of embryonic basal telencephalon, and examined the changes in cellular phenotypes resulting from blockade ofDlx-2 expression. Cells containingDlx-1, Dlx-2, andDlx-5 mRNAs are immature cells of the neuronal lineage expressing the microtubule-associated proteins (MAPs) MAP1B and MAP2, but not glial fibrillary acidic protein (GFAP). Treatment of these cells with antisense oligonucleotides targeted toDlx-2 caused a specific decrease ofDlx-2 mRNA and protein. This decrease in theDlx-2 gene product was associated with a decrease in the expression of MAP2, a protein localized in neuronal dendrites, along with a smaller decrease in the 200-kDa neurofilament subunit (NF-H). Proteins expressed preferentially in axons were unchanged. This reduction in MAP2 expression was associated with a decrease in dendrite outgrowth and an increased level of cell proliferation. None of these changes were elicited by antisense oligonucleotides targeted toDlx-1. We suggest that theDlx-2 gene product regulates two interrelated aspects of neuronal differentiation: the exit from the mitotic cycle and the capability to grow MAP2-positive dendrites. As such, this gene product may be important for the establishment of neuronal polarity, setting the stage for afferent synaptic connectivity.

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  1. Laurence Robel

    Present address: Department of Pedopsychiatry, Robert Debre Hospital, Paris, France

  2. Alaina J. James

    Present address: Department of Cell Biology, Rm M510, 1 Baylor Plaza, Baylor College of Medicine, 77030, Houston, TX

Authors and Affiliations

  1. Child Study Center, Yale University, 230 South Frontage Road, 06520, New Haven, CT

    Min Ding, Laurence Robel, Alaina J. James, James F. Leckman & Flora M. Vaccarino

  2. Nina Ireland Laboratory of Developmental Biology, Center for Neurobiology and Psychiatry, Department of Psychiatry, University of California, 94143-0984, San Francisco, CA

    David D. Eisenstat & John L. R. Rubenstein

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Ding, M., Robel, L., James, A.J. et al. Dlx-2 homeobox gene controls neuronal differentiation in primary cultures of developing basal ganglia. J Mol Neurosci 8, 93–113 (1997). https://doi.org/10.1007/BF02736776

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