{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:17:33Z","timestamp":1790461053740,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,11,4]]},"abstract":"<jats:p>\n                    Disrupted ERK1\/2 (\n                    <jats:italic>MAPK3<\/jats:italic>\n                    \/\n                    <jats:italic>MAPK1<\/jats:italic>\n                    ) MAPK signaling has been associated with several developmental syndromes in humans; however, mutations in\n                    <jats:italic>ERK1<\/jats:italic>\n                    or\n                    <jats:italic>ERK2<\/jats:italic>\n                    have not been described. We demonstrate haplo-insufficient ERK2 expression in patients with a novel \u22481 Mb micro-deletion in distal 22q11.2, a region that includes\n                    <jats:italic>ERK2<\/jats:italic>\n                    . These patients exhibit conotruncal and craniofacial anomalies that arise from perturbation of neural crest development and exhibit defects comparable to the DiGeorge syndrome spectrum. Remarkably, these defects are replicated in mice by conditional inactivation of\n                    <jats:italic>ERK2<\/jats:italic>\n                    in the developing neural crest. Inactivation of upstream elements of the ERK cascade (\n                    <jats:italic>B-Raf<\/jats:italic>\n                    and\n                    <jats:italic>C-Raf, MEK1<\/jats:italic>\n                    and\n                    <jats:italic>MEK2<\/jats:italic>\n                    ) or a downstream effector, the transcription factor serum response factor resulted in analogous developmental defects. Our findings demonstrate that mammalian neural crest development is critically dependent on a RAF\/MEK\/ERK\/serum response factor signaling pathway and suggest that the craniofacial and cardiac outflow tract defects observed in patients with a distal 22q11.2 micro-deletion are explained by deficiencies in neural crest autonomous ERK2 signaling.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0805239105","type":"journal-article","created":{"date-parts":[[2008,10,24]],"date-time":"2008-10-24T20:55:30Z","timestamp":1224881730000},"page":"17115-17120","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":162,"title":["Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development"],"prefix":"10.1073","volume":"105","author":[{"given":"Jason","family":"Newbern","sequence":"first","affiliation":[{"name":"Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhong","sequence":"additional","affiliation":[{"name":"Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasika S.","family":"Wickramasinghe","sequence":"additional","affiliation":[{"name":"The Solomon H. 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