SOX5 Controls the Sequential Generation of Distinct Corticofugal Neuron Subtypes

The molecular mechanisms controlling the development of distinct subtypes of neocortical projection neurons, and CNS neuronal diversity more broadly, are only now emerging. We report that the transcription factor SOX5 controls the sequential generation of distinct corticofugal neuron subtypes by pre...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2008-01, Vol.57 (2), p.232-247
Main Authors: Lai, Tina, Jabaudon, Denis, Molyneaux, Bradley J., Azim, Eiman, Arlotta, Paola, Menezes, Joao R.L., Macklis, Jeffrey D.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Bromodeoxyuridine - metabolism
Cell Count - methods
Cell Differentiation
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Cerebral Cortex - growth & development
DEVBIO
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - physiology
Electroporation - methods
Embryo, Mammalian
Embryos
Gene expression
Gene Expression Regulation, Developmental - physiology
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Mice
Mice, Transgenic
MOLNEURO
Nerve Tissue Proteins - metabolism
Neural Pathways - cytology
Neurons
Neurons - classification
Neurons - physiology
Nuclear Proteins - deficiency
Nuclear Proteins - physiology
Repressor Proteins - physiology
SOXD Transcription Factors
Stilbamidines - metabolism
Studies
Thalamus - cytology
Thalamus - embryology
Thalamus - growth & development
Transcription factors
Tumor Suppressor Proteins - deficiency
Tumor Suppressor Proteins - physiology
Ultrasonic imaging
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Summary:The molecular mechanisms controlling the development of distinct subtypes of neocortical projection neurons, and CNS neuronal diversity more broadly, are only now emerging. We report that the transcription factor SOX5 controls the sequential generation of distinct corticofugal neuron subtypes by preventing premature emergence of normally later-born corticofugal neurons. SOX5 loss-of-function causes striking overlap of the identities of the three principal sequentially born corticofugal neuron subtypes: subplate neurons, corticothalamic neurons, and subcerebral projection neurons. In Sox5 −/− cortex, subplate neurons aberrantly develop molecular hallmarks and connectivity of subcerebral projection neurons; corticothalamic neurons are imprecisely differentiated, while differentiation of subcerebral projection neurons is accelerated. Gain-of-function analysis reinforces the critical role of SOX5 in controlling the sequential generation of corticofugal neurons—SOX5 overexpression at late stages of corticogenesis causes re-emergence of neurons with corticofugal features. These data indicate that SOX5 controls the timing of critical fate decisions during corticofugal neuron production and thus subtype-specific differentiation and neocortical neuron diversity.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2007.12.023