Neural progenitor cells originating in the subventricular zone (SVZ) integrate into the neural circuitry that mediates olfactory learning and impacts habit formation. The SVZ produces new neurons throughout development and adulthood that are in part responsible for the life-long elaboration and refinement of the olfactor bulb cytoarchitecture. These new neurons migrate from the SVZ to the olfactory bulb via a pathway called the rostral migratory stream. However, the molecular mechanisms that guide these migrating cells to the olfactory bulb are poorly defined. Building on strong initial findings implicating ephrinB and EphB proteins in control of migration of cells within the rostral migratory steam, we have established novel assay systems that allow us to begin to define the exact role of astrocytes in adult migration. We propose three specific aims: Determine whether expression of ephrin-B2 in the astrocyte sheath constrains migration of adult neural progenitor cells within the rostral migratory steam. Determine whether EphB2 is required for astrocyte dependent-migration of adult neural progenitor cells in the rostral migratory steam. Determine whether astrocytes lining the rostral migratory steam constrain migration by activation of EphB2 in migrating neural progenitor cells. Because previous results have demonstrated progenitor cell proliferation is reduced in depression and EphB and ephrinB expression is altered by changes in neuronal activity our proposed studies will have board impact on the understanding of the basic biology of progenitor cell migration and the cellular-molecular mechanisms controlling pathophysiology.

Public Health Relevance

Building on our preliminary data, our proposal will examine newly defined roles that a set of proteins, EphBs and ephrinBs, have in the glial control of migration of progenitor cells from the subventricular zone to the olfactory bulb.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH100093-02
Application #
8690980
Study Section
Cellular and Molecular Biology of Glia Study Section (CMBG)
Program Officer
Panchision, David M
Project Start
2013-07-01
Project End
2018-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$387,500
Indirect Cost
$137,500
Name
Thomas Jefferson University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107