Satb2 Regulates Callosal Projection Neuron Identity in the Developing Cerebral Cortex

Alcamo, Elizabeth; Chirivella, Laura; Dautzenberg, Marcel; Dobreva, Gergana; Fariñas, Isabel; Grosschedl, Rudolf; McConnell, Susan K.

doi:10.1016/j.neuron.2007.12.012

Cited by 591 publications

(780 citation statements)

References 58 publications

(100 reference statements)

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“…indicating that precise levels of CSMN-specific genes are a fundamental requisite for correct differentiation of corticofugal neurons. Finally, because COUP-TFI and Fezf2 are both expressed in postmitotic neurons, it is possible that abnormal differentiation of CSMN and corticothalamic neurons in the absence of COUP-TFI occurs at a postmitotic level, as recently shown for other cortical transcriptional regulators (8,30,31,32).…”

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

confidence: 84%

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.

119

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: 84%

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.

119

130

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“…Pyramidal neurons can be subdivided into numerous subtypes, defined in vivo by a repertoire of molecular markers, identifying distinct layer-specific neuronal populations 7,[22][23][24] . To examine the diversity of the neuronal repertoire derived from ESCs in DDM plus cyclopamine, we studied the expression of a large set of layer-specific markers corresponding to the major subtypes of cortical neurons generated in vivo in the mouse (Fig.…”

Section: Sequential Cortical Neurogenesis From Escsmentioning

confidence: 99%

An intrinsic mechanism of corticogenesis from embryonic stem cells

Gaspard

Bouschet

Hourez

et al. 2008

Nature

577

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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“…SATB2 similarly binds to AT-rich DNA sequences to regulate gene expression, and is a key regulator of neuronal and skeletal development [65,66]. High SATB2 expression is also found in aggressive breast cancer with poor clinical outcome [67].…”

Section: The Role Of Nuclear Organization In Cancer 119mentioning

confidence: 99%

The role of nuclear organization in cancer

Lever¹,

Sheer²

2009

The Journal of Pathology

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The functional significance of changes in nuclear structure and organization in transformed cells remains one of the most enigmatic questions in cancer biology. In this review, we discuss relationships between nuclear organization and transcription in terms of the threedimensional arrangement of genes in the interphase cancer nucleus and the regulatory functions of nuclear matrix proteins. We also analyse the role of nuclear topology in the generation of gene fusions. We speculate that this type of multi-layered analysis will one day provide a framework for a more comprehensive understanding of the genetic origins of cancer and the identification of new therapeutic targets.

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Satb2 Regulates Callosal Projection Neuron Identity in the Developing Cerebral Cortex

Cited by 591 publications

References 58 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

An intrinsic mechanism of corticogenesis from embryonic stem cells

The role of nuclear organization in cancer

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