COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas

Armentano, Maria Francesca; Chou, Shen-Ju; Tomassy, Giulio Srubek; Leingärtner, Axel; O’Leary, Dennis D.M.; Studer, Michèle

doi:10.1038/nn1958

Cited by 229 publications

(336 citation statements)

References 33 publications

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“…Confirming this hypothesis, we found that even before grafting most ESC-derived neural progenitors expressed the CoupTFI (NR2F1) and CoupTFII (NR2F2) transcription factors (81.64 6 2.22% and 95.1 6 1.23%, respectively, Supplementary Fig. 8f, g), which are preferentially expressed in the embryonic occipital/visual cortex 34,35 .…”

Section: Cortical Axonal Projections Of Esc Neuronssupporting

confidence: 73%

An intrinsic mechanism of corticogenesis from embryonic stem cells

Gaspard

Bouschet

Hourez

et al. 2008

Nature

584

634

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The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.

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Section: Cortical Axonal Projections Of Esc Neuronssupporting

confidence: 73%

An intrinsic mechanism of corticogenesis from embryonic stem cells

Gaspard

Bouschet

Hourez

et al. 2008

Nature

584

634

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“…Our retrograde tracings from the spinal cord demonstrate that the tract originates largely from the corticothalamic neurons in layer mVI within the abnormally expanded motorized cortex (17). Thus, these misspecifed neurons may not be integrated into appropriate cortical motor neuronal networks, and therefore are unable to contribute to fine motor control.…”

mentioning

confidence: 89%

“…We next investigated how the increase in motor area size (17), and the reassignment of the corticospinal connectivity to layer VI corticothalamic neurons, might affect sensorimotor function in COUP-TFI adult mutant mice. We first investigated sensorimotor function by using an adhesive patch removal task (25), in which the mouse has to remove a piece of adhesive patch placed on each hindpaw.…”

Section: Coup-tfi Controls the Area-specific Timing Of Csmn Specificamentioning

confidence: 99%

“…As a striking illustration of such processes, CSMN are generated at a higher rate in the developing motor cortex than in sensory areas in mice (12), but the molecular mechanisms that control this area-specific differential production of CSMN are not known. The transcription factor COUP-TFI is particularly interesting in this regard, because it is expressed at different levels in presumptive sensory and motor cortices, and could thus underlie the striking cytoarchitectural differences between these two cortical areas (17,18). Using cortexspecific conditional loss-of-function of COUP-TFI, we have previously demonstrated that this transcription factor is critical for areal patterning by acting in sensory cortex to repress frontal/motor cortical area identity (17).…”

mentioning

confidence: 99%

“…The transcription factor COUP-TFI is particularly interesting in this regard, because it is expressed at different levels in presumptive sensory and motor cortices, and could thus underlie the striking cytoarchitectural differences between these two cortical areas (17,18). Using cortexspecific conditional loss-of-function of COUP-TFI, we have previously demonstrated that this transcription factor is critical for areal patterning by acting in sensory cortex to repress frontal/motor cortical area identity (17). COUP-TFI has also been shown to regulate neuronal differentiation (19) and, together with COUP-TFII, to control the timing of the switch of progenitor cells from neurogenesis to gliogenesis in the developing cortex (20).…”

mentioning

confidence: 99%

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Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

Tomassy

Leonibus

Jabaudon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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121

130

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Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise.arealization | subcerebral projection neurons | neocortex development | corticofugal neurons | nuclear receptor | behavior T he mammalian cerebral cortex, responsible for fine motor control and sensorimotor integration, is subdivided into functionally distinct areas that control motor functions and process distinct sensory modalities (1). Individual areas are distinguished by their cytoarchitecture, connectivity, physiology, and patterns of gene expression (2, 3). Each area is radially divided into six layers, and each layer consists of a variety of populations of neurons with distinctive morphologies, connectivity, and developmental programs of gene expression (4-9). In particular, layers VI and V contain corticofugal neurons, which send their axons to deep brain structures, such as the thalamus (corticothalamic neurons), the striatum (corticostriatal neurons), pons (corticopontine neurons), tectum (corticotectal neurons), and spinal cord (corticospinal motor neurons, CSMN) (7).The fate of neurons and laminar cytoarchitecture in each specific area determines their function: the adult primary motor cortex contains a large number of CSMN and has a thick layer V; the primary somatosensory area is characterized by a thick layer IV, where the neurons that receive relayed sensory inputs are located (10). The area-specific differences in neuronal fate and cytoarchitecture have been thought to result from late postmitotic events, e.g. selective postnatal pruning of axons (11), and premitotic events, such as the timing, rate, and duration of proliferation of precursors producing distinct projection neuron subtypes (12-16). As a striking illustration of such processes, CSMN are generated at a higher rate in the developing motor cortex than in sensory areas in mice (12), but the molecular mechanisms that control this area-specific differential production of CSMN are not known. The transcription factor COUP-TFI is particularly interestin...

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