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Title

SOX5 controls the sequential generation of distinct corticofugal neuron subtypes

Authors
Lai, Tina
Molyneaux, Bradley J.
Azim, Eiman
Arlotta, Paola
Menezes, Joao R L.
Macklis, Jeffrey D.
Published in Neuron. 2008, vol. 57, no. 2, p. 232-47
Abstract 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.
Keywords AnimalsAnimals, NewbornBromodeoxyuridine/metabolismCell Count/methodsCell DifferentiationCerebral Cortex/cytology/embryology/growth & developmentDNA-Binding Proteins/deficiency/physiologyElectroporation/methodsEmbryo, MammalianGene Expression Regulation, Developmental/physiologyGreen Fluorescent Proteins/genetics/metabolismMiceMice, TransgenicNerve Tissue Proteins/metabolismNeural Pathways/cytologyNeurons/classification/physiologyNuclear Proteins/deficiency/physiologyRepressor Proteins/physiologySOXD Transcription FactorsStilbamidines/metabolismThalamus/cytology/embryology/growth & developmentTumor Suppressor Proteins/deficiency/physiology
Identifiers
PMID: 18215621
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Structures
Research group Neurobiologie développementale et plasticité (880)
Citation
(ISO format)
LAI, Tina et al. SOX5 controls the sequential generation of distinct corticofugal neuron subtypes. In: Neuron, 2008, vol. 57, n° 2, p. 232-47. https://archive-ouverte.unige.ch/unige:2431

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Deposited on : 2009-08-13

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