Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo.
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.
Arlotta
Paola
P
MGH-HMS Center for Nervous System Repair, Departments of Neurosurgery and Neurology, Program in Neuroscience and Harvard Stem Cell Institute, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Molyneaux
Bradley J
BJ
Chen
Jinhui
J
Inoue
Jun
J
Kominami
Ryo
R
Macklis
Jeffrey D
JD
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020439:Growth Cones / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009044:Motor Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011712:Pyramidal Tracts / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D013477:Superior Colliculi / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C472865:Rit1 protein, mouse; D018631:ras Proteins