Neural-specific inactivation of ShcA functions results in anatomical disorganization of subventricular zone neural stem cell niche in the adult brain.

Abstract Shc(s) family of adaptor molecules has been implicated in several physiological functions. In particular, our previous studies have shown major roles in the mechanisms that control the transition from proliferating neural stem cells (NSCs) to postmitotic neurons in the mammalian brain. In the adult brain, ShcA expression is mainly restricted to a subpopulation of cells in the subventricular zone (SVZ) neurogenic area, enlightening a potential role for this molecule in the establishment/maintenance of this adult NSC niche. In order to investigate this matter, here we took advantage of Cre/lox technology with the purpose of interfering with (or delete) ShcA function in nestin-expressing neural progenitors in vivo . Our analyses revealed signs of anatomical disorganization in the adult brain at the boundary between the striatum and the corpus callosum and reduced thickness both at the ventricular level and through the rostral migratory stream. Analysis of cell proliferation and cell death unveiled a prominent reduction of the former and no substantial alterations of the latter. Ultrastructural studies showed SVZ anatomical disarray and manifest variation in the SVZ cell type composition. In conclusion, these results provide evidence for a role of ShcA in the assembly and/or maintenance of the SVZ NSC niche in the adult brain.