Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo

• DOI: 10.1016/j.neuron.2004.12.036
• Publication Date: 2005-01-20T14:21:14Z
• Authors: Paola Arlotta; Bradley J. Molyneaux; Jinhui Chen; Jun Inoue; Ryo Kominami; Jeffrey D. Macklis
• Keywords: Mice, Knockout; Motor Neurons; Superior Colliculi; 0303 health sciences; Neuroscience(all); Gene Expression Profiling; Growth Cones; Motor Cortex; Pyramidal Tracts; Gene Expression Regulation, Developmental; Cell Differentiation; Nerve Tissue Proteins; Corpus Callosum; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals, Newborn; ras Proteins; Animals; Nerve Growth Factors; Oligonucleotide Array Sequence Analysis; Transcription Factors

Within the vertebrate nervous system, the presence of many different lineages of neurons and glia complicates the molecular characterization of single neuronal populations. In order to elucidate molecular mechanisms underlying the specification and development of corticospinal motor neurons (CSMN), we purified CSMN at distinct stages of development in vivo and compared their gene expression to two other pure populations of cortical projection neurons: callosal projection neurons and corticotectal projection neurons. We found genes that are potentially instructive for CSMN development, as well as genes that are excluded from CSMN and are restricted to other populations of neurons, even within the same cortical layer. Loss-of-function experiments in null mutant mice for Ctip2 (also known as Bcl11b), one of the newly characterized genes, demonstrate that it plays a critical role in the development of CSMN axonal projections to the spinal cord in vivo, confirming that we identified central genetic determinants of the CSMN population.