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ID: 90: ADAM10 REGULATES STEMNESS OF ADULT NEURAL STEM CELLS BY MEDIATING THEIR POSITIONING WITHIN THE SVZ NICHE
  1. N McMillan
  1. Neurobiology, Stony Brook University, East Setauket, New York, United States

Abstract

The subventricular zone (SVZ) niche has been defined to have two distinct microenivroments, an apical compartment that is directly in contact with CSF and a basal compartment with a rich vascular network. Both these compartments regulate neural stem cell (NSC) properties via a diverse array of extrinsic cues by regulating both NSC-NSC and NSC-niche interactions. A majority of these signaling mechanisms are initiated by metalloproteinases. In this study, we investigated one such molecule, a disintegrin and metalloproteinase 10 (ADAM10) and its role in maintaining NSC properties. Using a conditional knockout, in which ADAM10 is specifically deleted in NSCs and NPCs (Nestin-CRE™/ADAM10fl/fl; denoted as KO) we noted altered contacts within the apical and basal compartments. BrdU pulse-chase studies demonstrated an increased number of long-term retaining BrdU NSCs in these KO mice. We also observed decreased BrdU label retaining neurons in the olfactory bulb in addition to a decreased neuroblast population in the SVZ indicating impaired neurogenesis in the KO mice. Intriguingly, we also observed cytoskeletal changes in NSCs and decreased migration of cells from the core of neurospheres derived from KO SVZ cells. This altered cell shape could intrinsically affect cell cycle progression. Taken together, this data suggests ADAM10 activity within the SVZ niche regulates NSC intrinsic properties and alters their cell cycle progression. Moreover, ADAM10 deletion appears to promote an aberrant self-renewal phenotype in NSCs preventing their differentiation. A more thorough understanding of how ADAM10 mediates these cellular changes and the underlying molecular mechanisms could be crucial in enhancing SVZ neurogenesis.

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