COUP-TFI Coordinates Cortical Patterning, Neurogenesis, and Laminar Fate and Modulates MAPK/ERK, AKT, and ß-Catenin Signaling

Faedo, Andrea; Tomassy, Giulio Srubek; Ruan, Youlin; Teichmann, Hannah; Krauß, Stefan; Pleasure, Samuel J.; Tsai, Sophia Y.; Tsai, Ming‐Jer; Studer, Michèle; Rubenstein, John L.R.

doi:10.1093/cercor/bhm238

Cited by 134 publications

(163 citation statements)

References 95 publications

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“…In the present study, we provide evidence that COUP-TFI is an upstream negative regulator of a CSMN differentiation program in corticofugal neurons, through repression of a genetic program of CSMN differentiation. First, during the period of corticofugal neuron birth and specification, an increased number of Fezf2-and CTIP2-positive neurons in COUP-TFI CKO mice are generated; second, COUP-TFI-deficient neurons in layers V and VI express abnormally high levels of Fezf2, CTIP2, Crim1, and Igfbp4; third, gain-of-function of COUP-TFI in a transgenic model shows decreased expression of Fezf2 and other layer V markers (19). An especially interesting aspect of these results is the abnormal differentiation of genuine CSMN in layer V of COUP-TFI CKO mice, including failure of these neurons to send projections to the spinal cord.…”

Section: Coup-tfi Is a Negative Regulator Of A Genetic Csmn Differentmentioning

confidence: 99%

“…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). Given the dual function of COUP-TFI in neuronal and areal specification, we hypothesized that COUP-TFI might control sensory area formation by repressing a "motorizing" genetic program of differentiation in neurons of the somatosensory cortex.…”

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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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Section: Coup-tfi Is a Negative Regulator Of A Genetic Csmn Differentmentioning

confidence: 99%

mentioning

confidence: 99%

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.

Self Cite

121

130

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“…3B). The roles of COUP-TFI in cortical development have been studied in germline and cortexspecific mutant mice, and have also been investigated by in vivo overexpression (Zhou et al 2001;Armentano et al 2007;Faedo et al 2008). In mice with a cortex-specific deletion of COUP-TFI, the expression of regional cortical plate markers Cdh8, Id2, Fezf2, and Efna5 revealed that the balance of area pattern was changed such that the majority of the cortex was transformed into motor cortex, and the somatosensory and visual areas were greatly reduced in size and located at the caudal pole of the structure (Fig.…”

Section: Fgf Signaling Establishes An Opposing Gradient Of the Caudalmentioning

confidence: 99%

“…The regulation of FGF signaling by COUP-TFI is less well understood. However, reduced levels of phospho-Erk1/2 have been reported in the neocortex of mice constitutively overexpressing COUP-TFI, indicating that COUP-TFI can negatively regulate FGF signaling (Faedo et al 2008). The ability of FGF to repress the expression of COUP-TFI indicates that the Fgf-signaling gradient is responsible for establishing the caudal-high to rostral-low gradient of COUP-TFI in the neocortex, in a manner analogous to that of the repression of dorsally expressed class II transcription factors in the spinal cord by the ventrally secreted morphogen sonic hedgehog (Briscoe and Ericson 2001).…”

Section: Fgf Signaling Establishes An Opposing Gradient Of the Caudalmentioning

confidence: 99%

Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex

Sansom

Livesey

2009

Cold Spring Harbor Perspectives in Biology

139

107

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In the developing brain, gradients are commonly used to divide neurogenic regions into distinct functional domains. In this article, we discuss the functions of morphogen and gene expression gradients in the assembly of the nervous system in the context of the development of the cerebral cortex. The cerebral cortex is a mammal-specific region of the forebrain that functions at the top of the neural hierarchy to process and interpret sensory information, plan and organize tasks, and to control motor functions. The mature cerebral cortex is a modular structure, consisting of anatomically and functionally distinct areas. Those areas of neurons are generated from a uniform neuroepithelial sheet by two forms of gradients: graded extracellular signals and a set of transcription factor gradients operating across the field of neocortical stem cells. Fgf signaling from the rostral pole of the cerebral cortex sets up gradients of expression of transcription factors by both activating and repressing gene expression. However, in contrast to the spinal cord and the early Drosophila embryo, these gradients are not subsequently resolved into molecularly distinct domains of gene expression. Instead, graded information in stem cells is translated into discrete, region-specific gene expression in the postmitotic neuronal progeny of the stem cells.

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“…Recently, it has been reported that the canonical Wnt pathway is also important for cellular proliferation in the ventricular zone and for fate determination in the cortex (Chenn and Walsh, 2002;Backman et al, 2005;Zhou et al, 2006;Woodhead et al, 2006;Machon et al, 2007). Furthermore, it was recently shown that neurogenesis in the cortex is directly correlated with a gradual decrease of canonical Wnt signaling (Machon et al, 2007;Faedo et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool

Solberg

Machoň

Krauß

2008

Developmental Dynamics

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Canonical Wnt signaling is crucial for the correct development of both cortical and hippocampal structures in the dorsal telencephalon. In this study, we examined the role of the canonical Wnt signaling in the dorsal telencephalon of mouse embryos at defined time periods by inhibition of the pathway with ectopic expression of Dkk1. Transgenic mice with the D6-driven Dkk1 gene exhibited reduced canonical Wnt signaling in the cortex and hippocampus. As a result, all hippocampal fields were reduced in size. Neurogenesis in the dentate gyrus was severely reduced both in the premigratory and migratory progenitor pool. The lower number of progenitors in the dentate gyrus was not rescued after migration to the subgranular zone and thus the dentate gyrus lacked the entire internal blade and a part of the external blade from postnatal to adult stages.

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COUP-TFI Coordinates Cortical Patterning, Neurogenesis, and Laminar Fate and Modulates MAPK/ERK, AKT, and ß-Catenin Signaling

Cited by 134 publications

References 95 publications

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

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

Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex

Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool

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