{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:19:47Z","timestamp":1777515587203,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM121625, R21HD090707"],"award-info":[{"award-number":["R01GM121625, R21HD090707"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The C. elegans vulva is an excellent model for the study of developmental biology and cell\u2013cell signaling. The developmental induction of vulval precursor cells (VPCs) to assume the 3\u00b0-3\u00b0-2\u00b0-1\u00b0-2\u00b0-3\u00b0 patterning of cell fates occurs with 99.8% accuracy. During C. elegans vulval development, an EGF signal from the anchor cell initiates the activation of RasLET-60 &gt; RafLIN-45 &gt; MEKMEK-2 &gt; ERKMPK-1 signaling cascade to induce the 1\u00b0 cell. The presumptive 1\u00b0 cell signals its two neighboring cells via NotchLIN-12 to develop 2\u00b0 cells. In addition, RasLET-60 switches effectors to RalGEFRGL-1 &gt; RalRAL-1 to promote 2\u00b0 fate. Shin et al. (2019) showed that RalGEFRGL-1 is a dual-function protein in VPCs fate patterning. RalGEFRGL-1 functions as a scaffold for PDKPDK-1 &gt; AktAKT-1\/2 modulatory signaling to promote 1\u00b0 fate in addition to propagating the RasLET-60 modulatory signal through RalRAL-1 to promote 2\u00b0 fate. The deletion of RalGEFRGL-1 increases the frequency of VPC patterning errors 15-fold compared to the wild-type control. We speculate that RalGEFRGL-1 represents an \u201cinsulated switch\u201d, whereby the promotion of one signaling activity curtails the promotion of the opposing activity. This property might increase the impact of the switch on fidelity more than two separately encoded proteins could. Understanding how developmental fidelity is controlled will help us to better understand the origins of cancer and birth defects, which occur in part due to the misspecification of cell fates.<\/jats:p>","DOI":"10.3390\/ijms21207610","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T09:02:03Z","timestamp":1602752523000},"page":"7610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Insulated Switches: Dual-Function Protein RalGEFRGL-1 Promotes Developmental Fidelity"],"prefix":"10.3390","volume":"21","author":[{"given":"Tam","family":"Duong","sequence":"first","affiliation":[{"name":"Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Texas A&amp;M University, Houston, TX 77030, USA"},{"name":"Department of Translational Medical Science, College of Medicine, Texas A&amp;M Health Science Center, Texas A&amp;M University, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal R.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Texas A&amp;M University, Houston, TX 77030, USA"},{"name":"Department of Translational Medical Science, College of Medicine, Texas A&amp;M Health Science Center, Texas A&amp;M University, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-7161","authenticated-orcid":false,"given":"David J.","family":"Reiner","sequence":"additional","affiliation":[{"name":"Institute of Biosciences and Technology, Texas A&amp;M Health Science Center, Texas A&amp;M University, Houston, TX 77030, USA"},{"name":"Department of Translational Medical Science, College of Medicine, Texas A&amp;M Health Science Center, Texas A&amp;M University, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.devcel.2008.09.011","article-title":"Plasticity and errors of a robust developmental system in different environments","volume":"15","author":"Braendle","year":"2008","journal-title":"Dev. 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