RT Journal Article SR Electronic T1 Haploinsufficiency of the psychiatric risk gene Cyfip1 causes abnormal postnatal hippocampal neurogenesis through microglial and Arp2/3 mediated actin dependent mechanisms JF bioRxiv FD Cold Spring Harbor Laboratory SP 417832 DO 10.1101/417832 A1 Niels Haan A1 Laura J Westacott A1 Jenny Carter A1 Michael J Owen A1 William P Gray A1 Jeremy Hall A1 Lawrence S Wilkinson YR 2020 UL http://biorxiv.org/content/early/2020/06/06/417832.abstract AB Genetic risk factors can significantly increase chances of developing psychiatric disorders, but the underlying biological processes through which this risk is effected remain largely unknown. Here we show that haploinsufficiency of Cyfip1, a candidate risk gene present in the pathogenic 15q11.2(BP1-BP2) deletion may impact on psychopathology via abnormalities in cell survival and migration of newborn neurons during postnatal hippocampal neurogenesis. We demonstrate that haploinsufficiency of Cyfip1 leads to increased numbers of adult born hippocampal neurons due to reduced apoptosis, without altering proliferation. We confirm this is due to a cell autonomous failure of microglia to induce apoptosis through the secretion of the appropriate factors. Furthermore, we show an abnormal migration of adult-born neurons due to altered Arp2/3 mediated actin dynamics. Together, our findings throw new light on how the genetic risk candidate Cyfip1 may influence the hippocampus, a brain region with strong evidence for involvement in psychopathology.Competing Interest StatementThe authors have declared no competing interest.