TWH Regulates the Development of Subsets of Spinal Cord Neurons

Thymocyte winged helix (TWH) is a putative transcription factor expressed in the developing neural tube. At midgestation, TWH expression identifies subsets of spinal cord motor neurons and interneurons. TWH-expressing motor neurons were restricted to specific spinal cord levels, distinguishing motor neurons at lumbar from those at cervical levels. To understand the developmental role of TWH, we replaced the TWH gene with the lacZ reporter gene and generated mice with a homozygous disruption of the TWH gene. TWH(-/-) mutant mice had increased perinatal mortality, retarded postnatal growth, and motor weakness. The TWH(-/-) mutation resulted in alterations in the sizes and position of different neuronal populations. Our results demonstrate that TWH plays a critical role in neuronal development and suggest that TWH regulates the early differentiation of neural progenitors.