{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:24:57Z","timestamp":1780511097956,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abnormalities in genes that regulate early brain development are known risk factors for neurodevelopmental disorders. <jats:italic>Engrailed\u20102<\/jats:italic> (<jats:italic>En2<\/jats:italic>) is a homeodomain transcription factor with established roles in cerebellar patterning. <jats:italic>En2<\/jats:italic> is highly expressed in the developing mid\u2010hindbrain region, and <jats:italic>En2<\/jats:italic> knockout (KO) mice exhibit major deficits in mid\u2010hindbrain structures. However, <jats:italic>En2<\/jats:italic> is also expressed in forebrain regions including the hippocampus, but its function is unknown. Previous studies have shown that the hippocampus of <jats:italic>En2<\/jats:italic>\u2010KO mice exhibits reductions in its volume and cell numbers due to aberrant neurogenesis. Aberrant neurogenesis is due, in part, to noncell autonomous effects, specifically, reductions of innervating norepinephrine fibers from the locus coeruleus. In this study, we investigate possible cell autonomous roles of <jats:italic>En2<\/jats:italic> in hippocampal neurogenesis. We examine proliferation, survival, and differentiation using cultures of hippocampal neurospheres of P7 wild\u2010type (WT) and <jats:italic>En2<\/jats:italic>\u2010KO hippocampal neural progenitor cells (NPCs). At 7\u00a0days, <jats:italic>En2<\/jats:italic>\u2010KO neurospheres were larger on average than WT spheres and exhibited 2.5\u2010fold greater proliferation and 2\u2010fold increase in apoptotic cells, similar to in vivo KO phenotype. Further, <jats:italic>En2<\/jats:italic>\u2010KO cultures exhibited 40% less cells with neurite projections, suggesting decreased differentiation. Lastly, reestablishing <jats:italic>En2<\/jats:italic> expression in <jats:italic>En2<\/jats:italic>\u2010KO NPCs rescued excess proliferation. These results indicate that <jats:italic>En2<\/jats:italic> functions in hippocampal NPCs by inhibiting proliferation and promoting survival and differentiation in a cell autonomous manner. More broadly, this study suggests that <jats:italic>En2<\/jats:italic> impacts brain structure and function in diverse regions outside of the mid\u2010hindbrain.<\/jats:p>","DOI":"10.1002\/dneu.22824","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T01:42:37Z","timestamp":1618450957000},"page":"724-735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>Engrailed\u20102<\/i> is a cell autonomous regulator of neurogenesis in cultured hippocampal neural stem cells"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-9834","authenticated-orcid":false,"given":"Madel","family":"Durens","sequence":"first","affiliation":[{"name":"School of Graduate Studies Rutgers, The State University of New Jersey Piscataway NJ USA"},{"name":"Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical School Rutgers, The State University of 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