Sohur US, Padmanabhan HK, Kotchetkov IS, Menezes JR, Macklis JD. 2014. Anatomic and molecular development of corticostriatal projection neurons in mice. Cerebral cortex (New York, N.Y. : 1991). 24(2):293-303. Pubmed: 23118198 DOI:10.1093/cercor/bhs342


Corticostriatal 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 (CStrPNi), projecting to the contralateral striatum, with their axons fully within the telencephalon (intratelencephalic), are a major population of CStrPN. CStrPNi are of particular interest developmentally because they share hodological and axon guidance characteristics of both callosal projection neurons (CPN) and corticofugal projection neurons (CFuPN); CStrPNi send axons contralaterally before descending into the contralateral striatum. The relationship of CStrPNi development to that of broader CPN and CFuPN populations remains unclear; evidence suggests that CStrPNi 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 CStrPNi in mice-their birth, maturation, projections, and expression of molecular developmental controls over projection neuron subtype identity.

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Jeffrey Macklis investigates molecular controls and mechanisms over neuron subtype specification, development, diversity, axon guidance-circuit formation, and pathology in the cerebral cortex. His lab seeks to apply developmental controls toward brain and spinal cord regeneration and directed differentiation for in vitro mechanistic modeling using human assembloids.

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