SOX5 Controls the Sequential Generation of Distinct Corticofugal Neuron Subtypes

MGH-HMS Center for Nervous System Repair, Department of Neurosurgery, Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA.
Neuron (Impact Factor: 15.05). 02/2008; 57(2):232-47. DOI: 10.1016/j.neuron.2007.12.023
Source: PubMed


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.

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Available from: Eiman Azim
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    • "Deep-layer (DL) neurons, which include layers 5 and 6, consist mainly of corticofugal projection neurons and project to subcortical targets. These neurons express transcription factors Fezf2, Ctip2, Tbr1, or Sox5 (Hevner et al., 2001; Arlotta et al., 2005; Kwan et al., 2008; Lai et al., 2008; Han et al., 2011; McKenna et al., 2011 "
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    • "Indeed, some transcription factors (e.g. SOX5, Tbr1 and Bhlhb5) that are expressed only in postmitotic neurons have been shown to modulate the laminar and areal identities of neuronal subtypes (Bedogni et al., 2010; Fishell and Hanashima, 2008; Han et al., 2011; Joshi et al., 2008; Lai et al., 2008). It is therefore plausible that neuronal subtype identities are specified at multiple steps before and after exiting the cell cycle. "
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    • "Other factors involved in neurogenesis during the CNS development include the Sox family transcription factors (Azim et al., 2009; Wegner and Stolt, 2005). Sox5 is a member of the Sox D group widely expressed in the developing forebrain and involved in the formation of the cephalic neural crest, in the control of cell cycle progression in neural progenitors, and of the sequential generation of distinct corticofugal neuron subtypes (Lai et al., 2008; Martinez-Morales et al., 2010; Perez- Alcala et al., 2004). Neurogenesis is a developmental process highly conserved across a wide range of species (Finlay and Darlington, 1995; Gomez-Skarmeta et al., 2006). "
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