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The Journal of Neuroscience, October 22, 2003, 23(29):9547-9556

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Cellular/Molecular
Cross-Repressive Interaction of the Olig2 and Nkx2.2 Transcription Factors in Developing Neural Tube Associated with Formation of a Specific Physical Complex

Tao Sun,1 * Hualing Dong,2 * Lizi Wu,3 Michael Kane,2 David H. Rowitch,1 and Charles D. Stiles2

Departments of 1Pediatric Oncology, 2Cancer Biology, and 3Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

In developing neural tube, the basic helix-loop-helix (bHLH) transcription factor Olig2 interacts with the homeodomain transcription factor Nkx2.2 at two distinct stages. During neuronogenesis, a cross-repressive interaction appears to establish the precise boundary between the p3 and pMN domains. At later times, a cooperative interaction is noted because Nkx2.2 promotes maturation of oligodendrocyte progenitor cells specified by expression of Olig2. We show here that the Olig2 protein can form a physical complex with Nkx2.2 protein in mammalian cells and yeast two-hybrid trap assay. This interaction is specific because Olig2 does not bind to a biologically irrelevant homeodomain transcription factor (Nkx6.1), and Nkx2.2 does not interact with a biologically irrelevant bHLH protein (NeuroD). Deletion mapping analysis suggests that formation of an Olig2-Nkx2.2 physical complex is insufficient for the induction of oligodendrocyte progenitors in developing spine; however, the protein-protein interaction observed might be important for the cross-repressive interaction between Olig2 and Nkx2.2 that helps to establish the pMN-p3 boundary in the developing spinal cord.

Key words: Nkx2.2; Olig2; homeodomain; bHLH; neural tube; neuronal subtype specification; oligodendrocyte; interneuron


Received April 28, 2003; revised August 26, 2003; accepted August 28, 2003.




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