Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (11): 2472-2483.doi: 10.4103/1673-5374.339007

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ADAM10 facilitates rapid neural stem cell cycling and proper positioning within the subventricular zone niche via JAMC/RAP1Gap signaling

Nadia McMillan1, 2, 3, Gregory W. Kirschen4, Sanket Desai2, Emma Xia2, Stella E. Tsirka2, *, #, Adan Aguirre2, #   

  1. 1Program in Neuroscience and Medical Scientist Training Program, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; 2Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; 3Department of Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA; 4Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, MD, USA
  • Online:2022-11-15 Published:2022-04-22
  • Contact: Stella E. Tsirka, PhD, styliani-anna.tsirka@stonybrook.edu.
  • Supported by:
    This work was supported by National Institutes of Health (NIH) Grants R01 RMH099384 (to AA) and T32GM008444 (to NM).

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Abstract: The mechanisms that regulate neural stem cell (NSC) lineage progression and maintain NSCs within different domains of the adult neural stem cell niche, the subventricular zone are not well defined. Quiescent NSCs are arranged at the apical ventricular wall, while mitotically activated NSCs are found in the basal, vascular region of the subventricular zone. Here, we found that ADAM10 (a disintegrin and metalloproteinase 10) is essential in NSC association with the ventricular wall, and via this adhesion to the apical domain, ADAM10 regulates the switch from quiescent and undifferentiated NSC to an actively proliferative and differentiating cell state. Processing of JAMC (junctional adhesion molecule C) by ADAM10 increases Rap1GAP activity. This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression. Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative properties of neural tissue.

Key words: ADAM10, adhesion, junctional adhesion molecule C, neural stem cells, neurogenesis, olfactory bulb, Rap1Gap, sub-ventricular zone