{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:19:54Z","timestamp":1791148794361,"version":"4.1.0"},"reference-count":67,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T00:00:00Z","timestamp":1599264000000},"content-version":"vor","delay-in-days":2227,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,1]]},"abstract":"<jats:p>Insulinoma associated 1 (Insm1) plays an important role in regulating the development of cells in the central and peripheral nervous systems, olfactory epithelium and endocrine pancreas. To better define the role of Insm1 in pancreatic endocrine cell development we generated mice with an Insm1GFPCre reporter allele and used them to study Insm1-expressing and null populations. Endocrine progenitor cells lacking Insm1 were less differentiated and exhibited broad defects in hormone production, cell proliferation and cell migration. Embryos lacking Insm1 contained greater amounts of a non-coding Neurog3 mRNA splice variant and had fewer Neurog3\/Insm1 co-expressing progenitor cells, suggesting that Insm1 positively regulates Neurog3. Moreover, endocrine progenitor cells that express either high or low levels of Pdx1, and thus may be biased towards the formation of specific cell lineages, exhibited cell type-specific differences in the genes regulated by Insm1. Analysis of the function of Ripply3, an Insm1-regulated gene enriched in the Pdx1-high cell population, revealed that it negatively regulates the proliferation of early endocrine cells. Taken together, these findings indicate that in developing pancreatic endocrine cells Insm1 promotes the transition from a ductal progenitor to a committed endocrine cell by repressing a progenitor cell program and activating genes essential for RNA splicing, cell migration, controlled cellular proliferation, vasculogenesis, extracellular matrix and hormone secretion.<\/jats:p>","DOI":"10.1242\/dev.104810","type":"journal-article","created":{"date-parts":[[2014,7,22]],"date-time":"2014-07-22T11:19:14Z","timestamp":1406027954000},"page":"2939-2949","source":"Crossref","is-referenced-by-count":72,"title":["<i>Insm1<\/i> promotes endocrine cell differentiation by modulating the expression of a network of genes that includes <i>Neurog3<\/i> and <i>Ripply3<\/i>"],"prefix":"10.1242","volume":"141","author":[{"given":"Anna B.","family":"Osipovich","sequence":"first","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoming","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Cornell University, Ithaca, NY 14850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Manduchi","sequence":"additional","affiliation":[{"name":"Penn Center for Bioinformatics, Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Gangula","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan B.","family":"Hipkens","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judsen","family":"Schneider","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science, Kitasato University School of Medicine, Sagamihara, 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Christian J.","family":"Stoeckert","sequence":"additional","affiliation":[{"name":"Penn Center for Bioinformatics, Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Takada","sequence":"additional","affiliation":[{"name":"Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Magnuson","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021052800022036800_DEV104810C1","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1101\/gad.12.12.1763","article-title":"beta-cell-specific inactivation of the mouse Ipf1\/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes","volume":"12","author":"Ahlgren","year":"1998","journal-title":"Genes Dev."},{"key":"2021052800022036800_DEV104810C2","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.gep.2011.08.003","article-title":"Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas","volume":"11","author":"Begum","year":"2011","journal-title":"Gene Expr. 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