Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Amino Acids / metabolism
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Animals
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Animals, Newborn
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Annexin A2 / genetics
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Annexin A2 / metabolism
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Apoptosis Regulatory Proteins / metabolism
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Bromodeoxyuridine / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Count / methods
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Death / physiology
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Cell Differentiation / physiology*
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Cell Movement / physiology
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
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Embryo, Mammalian
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Forkhead Transcription Factors / metabolism
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Gene Expression Regulation, Developmental / physiology*
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Green Fluorescent Proteins / biosynthesis
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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In Situ Nick-End Labeling / methods
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Motor Neurons / cytology
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Motor Neurons / physiology*
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Neocortex / cytology*
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Neocortex / growth & development
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Nuclear Proteins / metabolism
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POU Domain Factors / genetics
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POU Domain Factors / metabolism
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Phosphopyruvate Hydratase / metabolism
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Pyramidal Tracts / physiology*
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Repressor Proteins / metabolism
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S100 Proteins / genetics
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S100 Proteins / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Aatf protein, mouse
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Amino Acids
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Annexin A2
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Apoptosis Regulatory Proteins
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Carrier Proteins
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Cell Cycle Proteins
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CtIP protein, mouse
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Cux2 protein, mouse
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DNA-Binding Proteins
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Forkhead Transcription Factors
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Foxp2 protein, mouse
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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POU Domain Factors
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Plxnd1 protein, mouse
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Ppp1r1b protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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Repressor Proteins
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S100 Proteins
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S100 calcium binding protein A10
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Tumor Suppressor Proteins
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Zfp312 protein, mouse
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dolaisoleucine
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Pou3f2 protein, mouse
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Green Fluorescent Proteins
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Phosphopyruvate Hydratase
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Bromodeoxyuridine