Person: Sohur, Usharbudh
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Sohur
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Usharbudh
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Sohur, Usharbudh
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Publication Lmo4 and Clim1 progressively delineate cortical projection neuron subtypes during development(Oxford University Press (OUP), 2009) Azim, Eiman; Shnider, Sara J.; Cederquist, Gustav Y.; Sohur, Usharbudh; Macklis, JeffreyMolecular controls over the development of the exceptional neuronal subtype diversity of the cerebral cortex are now beginning to be identified. The initial subtype fate decision early in the life of a neuron, and the malleability of this fate when the balance of key postmitotic signals is modified, reveals not only that a neuron is deterministically set on a general developmental path at its birth, but also that this program must be precisely executed during postmitotic differentiation. Here, we show that callosal projection neurons (CPN) and subcerebral projection neurons (subcerebral PN) in layer V of the neocortex share aspects of molecular identity after their birth that are progressively resolved during differentiation. The LIM-homeodomain-related genes Lmo4 and Clim1 are initially expressed by both CPN and subcerebral PN in layer V, and only during mid to late differentiation does expression of Lmo4 and Clim1 become largely segregated into distinct neuronal subtypes. This progressive postmitotic resolution of molecular identity reveals similarities and possibly shared evolutionary origin between layer V CPN and subcerebral PN, and provides insight into how and when these neuronal subtypes achieve their distinct identities during cortical development.Publication Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice(Oxford University Press, 2013-03-18) Sohur, Usharbudh; Padmanabhan, Hari; Kotchetkov, Ivan S.; Menezes, Joao R.L.; Macklis, JeffreyCorticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally, behaviorally, and clinically important population of neocortical neurons. Little is known about their development. “Intratelencephalic” CStrPN \((CStrPN_i)\), projecting to the contralateral striatum, with their axons fully within the telencephalon (intratelencephalic), are a major population of CStrPN. \(CStrPN_i\) are of particular interest developmentally because they share hodological and axon guidance characteristics of both callosal projection neurons (CPN) and corticofugal projection neurons (CFuPN); \(CStrPN_i\) send axons contralaterally before descending into the contralateral striatum. The relationship of \(CStrPN_i\) development to that of broader CPN and CFuPN populations remains unclear; evidence suggests that \(CStrPN_i\) might be evolutionary “hybrids” between CFuPN and deep layer CPN—in a sense “chimeric” with both callosal and corticofugal features. Here, we investigated the development of \(CStrPN_i\) in mice—their birth, maturation, projections, and expression of molecular developmental controls over projection neuron subtype identity.Publication Developmental Controls are Re-Expressed during Induction of Neurogenesis in the Neocortex of Young Adult Mice(Frontiers Research Foundation, 2012) Sohur, Usharbudh; Arlotta, Paola; Macklis, JeffreyWhether induction of low-level neurogenesis in normally non-neurogenic regions of the adult brain mimics aspects of developmental neurogenesis is currently unknown. Previously, we and others identified that biophysically induced, neuron subtype-specific apoptosis in mouse neocortex results in induction of neurogenesis of limited numbers of subtype-appropriate projection neurons with axonal projections to either thalamus or spinal cord, depending on the neuron subtype activated to undergo targeted apoptosis. Here, we test the hypothesis that developmental genes from embryonic corticogenesis are re-activated, and that some of these genes might underlie induction of low-level adult neocortical neurogenesis. We directly investigated this hypothesis via microarray analysis of microdissected regions of young adult mouse neocortex undergoing biophysically activated targeted apoptosis of neocortical callosal projection neurons. We compared the microarray results identifying differentially expressed genes with public databases of embryonic developmental genes. We find that, following activation of subtype-specific neuronal apoptosis, three distinct sets of normal developmental genes are selectively re-expressed in neocortical regions of induced neurogenesis in young adult mice: (1) genes expressed by subsets of progenitors and immature neurons in the developing ventricular and/or subventricular zones; (2) genes normally expressed by developmental radial glial progenitors; and (3) genes involved in synaptogenesis. Together with previous results, the data indicate that at least some developmental molecular controls over embryonic neurogenesis can be re-activated in the setting of induction of neurogenesis in the young adult neocortex, and suggest that some of these activate and initiate adult neuronal differentiation from endogenous progenitor populations. Understanding molecular mechanisms contributing to induced adult neurogenesis might enable directed CNS repair.