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Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues. HMMR over-expression in immortalized cancer cells induces phenotypes consistent with an increase in active Ran including defects in spindle orientation. These data identify an essential role for HMMR in the PLK1-dependent regulatory pathway that orients progenitor cell division and supports neural development.<\/jats:p>","DOI":"10.7554\/elife.28672","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T08:00:11Z","timestamp":1507622411000},"source":"Crossref","is-referenced-by-count":56,"title":["HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7594-2137","authenticated-orcid":true,"given":"Marisa","family":"Connell","sequence":"first","affiliation":[{"name":"Department of Paediatrics, University of British Columbia, Vancouver, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of British Columbia, Vancouver, 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