{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:02:26Z","timestamp":1775624546225,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T00:00:00Z","timestamp":1345075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> GDNF\/RET and Endothelin\u20103 (ET\u20103)\/EDNRB regulate survival, differentiation, migration, and proliferation of neural crest\u2010derived cells. Although several RET and EDNRB signalling mediators have been characterized, most of the genes targeted by these two pathways are still largely unknown. We focused our study on apolipoprotein B (<jats:italic>APOB<\/jats:italic>) as a novel target gene of the RET and EDNRB pathways, based on previous data obtained using a <jats:italic>Caenorhabditis elegans<\/jats:italic> strain mutant for the homologue of mammalian <jats:italic>ECE1<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> Molecular and cellular studies of <jats:italic>Apob<\/jats:italic> were performed in the murine Neuro2a cells, an <jats:italic>in vitro<\/jats:italic> model for studying neural crest\u2010derived cell development, along with a mouse knock\u2010in for the Hirschsprung\u2010associated mutation <jats:italic>Ret<\/jats:italic><jats:sup><jats:italic>C620R<\/jats:italic><\/jats:sup>. Silencing for <jats:italic>Apob<\/jats:italic> and <jats:italic>Ret<\/jats:italic> has been performed via shRNA.<\/jats:p><jats:p><jats:bold>Key Results\u2002<\/jats:bold> GDNF\/RET and ET\u20103\/EDNRB cooperated in inducing neuronal differentiation resulting in <jats:italic>Apob<\/jats:italic> activation in Neuro2a cell line. <jats:italic>Apob<\/jats:italic> expression was downregulated in mouse embryos homozygous for the <jats:italic>Ret<\/jats:italic><jats:sup><jats:italic>C620R<\/jats:italic><\/jats:sup> mutation and presenting a severe Hirschsprung phenotype. <jats:italic>Ret<\/jats:italic> silencing prevented <jats:italic>Apob<\/jats:italic> expression increase. MAPK P38 kinase activation evoked <jats:italic>Apob<\/jats:italic> expression via GDNF\/RET signalling in Neuro2a cells. A p53\u2010dependent repressor element in <jats:italic>Apob<\/jats:italic> promoter resulted in a reduced <jats:italic>Apob<\/jats:italic> expression. Silencing of <jats:italic>Apob<\/jats:italic> reduced HuD protein expression.<\/jats:p><jats:p><jats:bold>Conclusions &amp; Inferences\u2002<\/jats:bold>  <jats:italic>Apob<\/jats:italic> is a novel downstream target of the RET\/EDNRB pathways with a role in neuronal survival and maintenance, as indicated by its effect on HuD expression. Our data provide a conceptual framework to investigate and establish the role of APOB gene in severe gut dysmotility.<\/jats:p>","DOI":"10.1111\/j.1365-2982.2012.01998.x","type":"journal-article","created":{"date-parts":[[2012,8,16]],"date-time":"2012-08-16T05:35:44Z","timestamp":1345095344000},"source":"Crossref","is-referenced-by-count":10,"title":["Apolipoprotein B is a new target of the GDNF\/RET and ET\u20103\/EDNRB signalling pathways"],"prefix":"10.1111","volume":"24","author":[{"given":"C.","family":"Evangelisti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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