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Caenorhabditis elegans hermaphrodites are somatic females that have a two-armed, U-shaped gonad that connects to the vulva at the midbody. The outgrowth of each gonad arm from the somatic gonad primordium is led by two female distal tip cells (fDTCs), while the anchor cell (AC) remains stationary and central to coordinate uterine and vulval development. The bHLH protein HLH-2 and its dimerization partners LIN-32 and HLH-12 had previously been shown to be required for fDTC specification. Here, we show that ectopic expression of both HLH-12 and LIN-32 in cells with AC potential transiently transforms them into fDTC-like cells. Furthermore, hlh-12 was known to be required for the fDTCs to sustain gonad arm outgrowth. Here, we show that ectopic expression of HLH-12 in the normally stationary AC causes displacement from its normal position and that displacement likely results from activation of the leader program of fDTCs because it requires genes necessary for gonad arm outgrowth. Thus, HLH-12 is both necessary and sufficient to promote gonadal regulatory cell migration. As differences in female gonadal morphology of different nematode species reflect differences in the fate or migratory properties of the fDTCs or of the AC, we hypothesized that evolutionary changes in the expression of hlh-12 may underlie the evolution of such morphological diversity. However, we were unable to identify an hlh-12 ortholog outside of Caenorhabditis. Instead, by performing a comprehensive phylogenetic analysis of all Class II bHLH proteins in multiple nematode species, we found that hlh-12 evolved within the Caenorhabditis clade, possibly by duplicative transposition of hlh-10. Our analysis suggests that control of gene regulatory hierarchies for gonadogenesis can be remarkably plastic during evolution without adverse phenotypic consequence.<\/jats:p>","DOI":"10.1093\/genetics\/iyab127","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T17:36:12Z","timestamp":1630690572000},"source":"Crossref","is-referenced-by-count":4,"title":["<i>hlh-12<\/i>, a gene that is necessary and sufficient to promote migration of gonadal regulatory cells in<i>Caenorhabditis elegans<\/i>, evolved within the<i>Caenorhabditis<\/i>clade"],"prefix":"10.1093","volume":"219","author":[{"given":"Hana E","family":"Littleford","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1588-4884","authenticated-orcid":false,"given":"Karin","family":"Kiontke","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Developmental Genetics, New York University, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6940-7544","authenticated-orcid":false,"given":"David H A","family":"Fitch","sequence":"additional","affiliation":[{"name":"Department of Biology, Center for Developmental Genetics, New York University, New York, NY 10003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7180-3706","authenticated-orcid":false,"given":"Iva","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027, 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