{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:42:01Z","timestamp":1791319321829,"version":"4.3.1"},"reference-count":40,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[1998,6,15]],"date-time":"1998-06-15T00:00:00Z","timestamp":897868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The endocrine pancreas is organized into clusters of cells called islets of Langerhans comprising four well-defined cell types: \u03b1, \u03b2, \u03b4 and PP cells. While recent genetic studies indicate that islet development depends on the function of an integrated network of transcription factors, the specific roles of these factors in early cell-type specification and differentiation remain elusive. Nkx2.2 is a member of the mammalian NK2 homeobox transcription factor family that is expressed in the ventral CNS and the pancreas. Within the pancreas, we demonstrate that Nkx2.2 is expressed in \u03b1, \u03b2 and PP cells, but not in \u03b4 cells. In addition, we show that mice homozygous for a null mutation of Nkx2.2 develop severe hyperglycemia and die shortly after birth.<\/jats:p>\n               <jats:p>Immunohistochemical analysis reveals that the mutant embryos lack insulin-producing \u03b2 cells and have fewer glucagon-producing \u03b1 cells and PP cells. Remarkably, in the mutants there remains a large population of islet cells that do not produce any of the four endocrine hormones. These cells express some \u03b2 cell markers, such as islet amyloid polypeptide and Pdx1, but lack other definitive \u03b2 cell markers including glucose transporter 2 and Nkx6.1. We propose that Nkx2.2 is required for the final differentiation of pancreatic \u03b2 cells, and in its absence, \u03b2 cells are trapped in an incompletely differentiated state.<\/jats:p>","DOI":"10.1242\/dev.125.12.2213","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:13:13Z","timestamp":1619406793000},"page":"2213-2221","source":"Crossref","is-referenced-by-count":520,"title":["Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic \u03b2 cells"],"prefix":"10.1242","volume":"125","author":[{"given":"L.","family":"Sussel","sequence":"first","affiliation":[{"name":"Nina Ireland Laboratory of Developmental Neurobiology 1 , Department of Psychiatry, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kalamaras","sequence":"additional","affiliation":[{"name":"2 Hormone Research Institute, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Hartigan-O\u2019Connor","sequence":"additional","affiliation":[{"name":"Nina Ireland Laboratory of Developmental Neurobiology 1 , Department of Psychiatry, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Meneses","sequence":"additional","affiliation":[{"name":"Department of Obstetrics 4 , Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. A.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics 4 , Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L. 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