Abstract
The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neural progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexity and spine development through β1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain.
Highlights
The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems
Immunohistochemistry showed that expression of plexinC1 in the dentate gyrus (DG) GCL is confined to cells located in the subgranular zone (SGZ) (Supplementary Fig. 1c)
Most NeuN þ mature granule cells (GCs) did not express plexinC1, while plexinC1 þ cells only rarely displayed NeuN signals (Fig. 1f–h). These results indicate that in the neurogenic niche of the DG plexinC1 is mostly confined to early progenitor cells, including RGLs and early IPCs, independent of their proliferation state (Fig. 1i)
Summary
The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain. Many of the key factors required for the regulation of aNPC proliferation in the SGZ have been identified, much less is known about the extracellular molecular signals that control the morphological development and integration of nGCs. Here we report that, in the adult mouse hippocampus, expression of plexinC1 is restricted to the SGZ and is largely confined to early progenitor cells. Our data reveal a novel role for Sema7A in the adult brain, implicate semaphorins and plexins in the control of cell proliferation during adult hippocampal neurogenesis, and provide an example of how a single guidance cue can regulate multiple stages of adult neurogenesis via two, stage-specific, distinct receptors
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