Fezl is required for the birth and specification of corticospinal motor neurons.
The molecular mechanisms controlling the differentiation of neural progenitors into distinct subtypes of neurons during neocortical development are unknown. Here, we report that Fezl is required for the specification of corticospinal motor neurons and other subcerebral projection neurons, which are absent from Fezl null mutant neocortex. There is neither an increase in cell death in Fezl(-/-) cortex nor abnormalities in migration, indicating that the absence of subcerebral projection neurons is due to a failure in fate specification. In striking contrast, other neuronal populations in the same and other cortical layers are born normally. Overexpression of Fezl results in excess production of subcerebral projection neurons and arrested migration of these neurons in the germinal zone. These data indicate that Fezl plays a central role in the specification of corticospinal motor neurons and other subcerebral projection neurons, controlling early decisions regarding lineage-specific differentiation from neural progenitors.
Molyneaux
Bradley J
BJ
MGH-HMS Center for Nervous System Repair, Department of Neurosurgery, Program in Neuroscience and Harvard Stem Cell Institute, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Arlotta
Paola
P
Hirata
Tustomu
T
Hibi
Masahiko
M
Macklis
Jeffrey D
JD
D000367:Age Factors; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004622:Embryo, Mammalian; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D019579:Neocortex / Q000166:cytology* / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D050809:POU Domain Factors / Q000235:genetics / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011712:Pyramidal Tracts / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
D000596:Amino Acids; D017306:Annexin A2; D051017:Apoptosis Regulatory Proteins; D001973:Bromodeoxyuridine; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D050809:POU Domain Factors; D010751:Phosphopyruvate Hydratase; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012097:Repressor Proteins; D009418:S100 Proteins; D025521:Tumor Suppressor Proteins; D000099248:S100 Calcium Binding Protein A10; C417216:Aatf protein, mouse; C501070:RBBP8 protein, mouse; C101672:Cux2 protein, mouse; C432918:Foxp2 protein, mouse; C473552:Plxnd1 protein, mouse; C497929:Ppp1r1b protein, mouse; C412364:Zfp312 protein, mouse; C098463:dolaisoleucine; C074066:Pou3f2 protein, mouse