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  • Ctip1 Regulates the Balance between Specification of Distinct Projection Neuron Subtypes in Deep Cortical Layers CELL REPORTS Woodworth, M. B., Greig, L. C., Liu, K. X., Ippolito, G. C., Tucker, H. O., Macklis, J. D. 2016; 15 (5): 999-1012

    Abstract

    The molecular linkage between neocortical projection neuron subtype and area development, which enables the establishment of functional areas by projection neuron populations appropriate for specific sensory and motor functions, is poorly understood. Here, we report that Ctip1 controls precision of neocortical development by regulating subtype identity in deep-layer projection neurons. Ctip1 is expressed by postmitotic callosal and corticothalamic projection neurons but is excluded over embryonic development from corticospinal motor neurons, which instead express its close relative, Ctip2. Loss of Ctip1 function results in a striking bias in favor of subcerebral projection neuron development in sensory cortex at the expense of corticothalamic and deep-layer callosal development, while misexpression of Ctip1 in vivo represses subcerebral gene expression and projections. As we report in a paired paper, Ctip1 also controls acquisition of sensory area identity. Therefore, Ctip1 couples subtype and area specification, enabling specific functional areas to organize precise ratios of appropriate output projections.

    View details for DOI 10.1016/j.celrep.2016.03.064

    View details for PubMedID 27117402

  • Ctip1 Controls Acquisition of Sensory Area Identity and Establishment of Sensory Input Fields in the Developing Neocortex NEURON Greig, L. C., Woodworth, M. B., Greppi, C., Macklis, J. D. 2016; 90 (2): 261-277

    Abstract

    While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive "sensory field" in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development.

    View details for DOI 10.1016/j.neuron.2016.03.008

    View details for Web of Science ID 000374504400009

    View details for PubMedID 27100196

    View details for PubMedCentralID PMC4873772

  • Molecular logic of neocortical projection neuron specification, development and diversity NATURE REVIEWS NEUROSCIENCE Greig, L. C., Woodworth, M. B., Galazo, M. J., Padmanabhan, H., Macklis, J. D. 2013; 14 (11): 755-769

    Abstract

    The sophisticated circuitry of the neocortex is assembled from a diverse repertoire of neuronal subtypes generated during development under precise molecular regulation. In recent years, several key controls over the specification and differentiation of neocortical projection neurons have been identified. This work provides substantial insight into the 'molecular logic' underlying cortical development and increasingly supports a model in which individual progenitor-stage and postmitotic regulators are embedded within highly interconnected networks that gate sequential developmental decisions. Here, we provide an integrative account of the molecular controls that direct the progressive development and delineation of subtype and area identity of neocortical projection neurons.

    View details for DOI 10.1038/nrn3586

    View details for Web of Science ID 000325918900008

    View details for PubMedID 24105342

    View details for PubMedCentralID PMC3876965

  • SnapShot: Cortical Development CELL Woodworth, M. B., Greig, L. C., Kriegstein, A. R., Macklis, J. D. 2012; 151 (4): 918-?

    View details for DOI 10.1016/j.cell.2012.10.004

    View details for Web of Science ID 000310921200023

    View details for PubMedID 23141546

    View details for PubMedCentralID PMC3694327