Person:
Xu, Zhaoying

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Xu

First Name

Zhaoying

Name

Xu, Zhaoying

Filters

20161

Settings

Author's Publications: search.filters.isAuthorOfPublication.1dc6302c-a5f9-45f9-b2bf-b31540b7ff7a

Search Results

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Publication
    Subtype-Specific Corticostriatal Projection Neuron Developmental Gene Expression and Corticospinal Expression of the Paroxysmal Nonkinesigenic Dyskinesia Gene
    (2016-09-15) Xu, Zhaoying; Arlotta, Paola; Macklis, Jeffrey; Lehtinen, Maria; Harwell, Corey; Schwob, James
    The mammalian neocortex is responsible for motor control, integration of sensory information, perception, cognitive function, and consciousness. It is complex, yet highly organized, with six layers containing broad classes of excitatory projection neurons (along with interneurons) with diverse subtype and area identities. Corticostriatal projection neurons (CStrPN) are the major cortical efferent neurons connecting the cerebral cortex to the striatum of the basal ganglia, and are critically involved in motor planning, execution, movement control, learning, and cognitive functions. As the predominant type of CStrPN, intratelencephalic CStrPN (CStrPNi) project axons across the hemispheres to innervate contralateral striatum, and degenerate selectively (along with striatal projection neurons) in Huntington’s disease. While much progress has been made toward elucidating the anatomical connectivity, electrophysiological properties, and neuromodulatory effects of CStrPN, specific genes and molecules expressed by CStrPNi during their development and maturation have remained unknown. Work presented in this dissertation identified genes with enriched CStrPNi expression from labeled, isolated, and FACS-purified CStrPNi compared with the closely related callosal projection neurons (CPN). I then used the temporal gene expression profiles to progressively filter and identify a selected set of relatively subtype-specific genes highly expressed by CStrPNi at distinct stages: Gfra2 and Nhlrc1 expressed during early CStrPNi development; Foxp1 and Cxcr4 expressed during intermediate stages of CStrPNi development; and Scube1 during late stage of CStrPNi development. I also characterize, at a subtype-specific level, the developmental expression of a recently developed, candidate CStrPNi-specific Cre driver line, Tlx3-BAC-Cre (PL56), which enables future in-depth investigation of CStrPNi development and circuitry. Together, these data constitute the first set of genes known to be expressed by CStrPNi during cortical development. In a second project, I focus on the human paroxysmal nonkinesigenic dyskinesia gene, Pnkd, whose mutation causes this severe movement disorder. I investigate the developmental and subtype specificity of Pnkd expression. The other type of CStrPN, pyramidal type CStrPN (CStrPNp), are subcerebral projection neurons (SCPN) - corticospinal motor neurons (CSMN) or cortico-brainstem projection neurons - that extend axon collaterals to innervate the ipsilateral striatum and multiple other targets. I demonstrate that Pnkd expression is specially enriched in CSMN and other SCPN, implicating PNKD as potentially functioning in corticostriatal circuitry. These results provide new insights into the pathophysiology of this early childhood onset, severe human neurological movement disorder.