1. Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord.
- Author
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Iulianella A, Sharma M, Vanden Heuvel GB, and Trainor PA
- Subjects
- Animals, Base Sequence, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Cycle, DNA Primers genetics, Embryo Culture Techniques, Embryonic Stem Cells cytology, Embryonic Stem Cells metabolism, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins genetics, Interneurons cytology, Mice, Mice, Mutant Strains, Mice, Transgenic, Neurogenesis genetics, Neurogenesis physiology, Receptor, Notch1 genetics, Signal Transduction genetics, Signal Transduction physiology, Spinal Cord cytology, Spinal Cord metabolism, Homeodomain Proteins metabolism, Interneurons metabolism, Receptor, Notch1 metabolism, Spinal Cord embryology
- Abstract
Obtaining the diversity of interneuron subtypes in their appropriate numbers requires the orchestrated integration of progenitor proliferation with the regulation of differentiation. Here we demonstrate through loss-of-function studies in mice that the Cut homeodomain transcription factor Cux2 (Cutl2) plays an important role in regulating the formation of dorsal spinal cord interneurons. Furthermore, we show that Notch regulates Cux2 expression. Although Notch signaling can be inhibitory to the expression of proneural genes, it is also required for interneuron formation during spinal cord development. Our findings suggest that Cux2 might mediate some of the effects of Notch signaling on interneuron formation. Together with the requirement for Cux2 in cell cycle progression, our work highlights the mechanistic complexity in balancing neural progenitor maintenance and differentiation during spinal cord neurogenesis. more...
- Published
- 2009
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