{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:23:40Z","timestamp":1791271420018,"version":"4.1.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Dev Biol"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Nkx2.2 and Arx represent key transcription factors implicated in the specification of islet cell subtypes during pancreas development. Mice deficient for <jats:italic>Arx<\/jats:italic> do not develop any alpha-cells whereas beta- and delta-cells are found in considerably higher numbers. In <jats:italic>Nkx2.2<\/jats:italic> mutant animals, alpha- and beta-cell development is severely impaired whereas a ghrelin-expressing cell population is found augmented.<\/jats:p>\n            <jats:p>Notably, <jats:italic>Arx<\/jats:italic> transcription is clearly enhanced in <jats:italic>Nkx2.2<\/jats:italic>-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of <jats:italic>Nkx2.2\/Arx<\/jats:italic> single- and double-mutants but also of <jats:italic>Pax6<\/jats:italic>-deficient animals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We show that most of the ghrelin<jats:sup>+<\/jats:sup> cells emerging in pancreata of <jats:italic>Nkx2.2<\/jats:italic>- and <jats:italic>Pax6<\/jats:italic>-deficient mice, express the alpha-cell specifier Arx, but also additional beta-cell related genes. In <jats:italic>Nkx2.2<\/jats:italic>-deficient mice, Arx directly co-localizes with iAPP, PC1\/3 and Pdx1 suggesting an Nkx2.2-dependent control of <jats:italic>Arx<\/jats:italic> in committed beta-cells. The combined loss of <jats:italic>Nkx2.2<\/jats:italic> and <jats:italic>Arx<\/jats:italic> likewise results in the formation of a hyperplastic ghrelin<jats:sup>+<\/jats:sup> cell population at the expense of mature alpha- and beta-cells. Surprisingly, such <jats:italic>Nkx2.2<\/jats:italic>\n              <jats:sup>\n                <jats:italic>-\/-<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Arx<\/jats:italic>\n              <jats:sup>\n                <jats:italic>-<\/jats:italic>\n              <\/jats:sup> ghrelin<jats:sup>+<\/jats:sup> cells also express the somatostatin hormone.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our data indicate that Nkx2.2 acts by reinforcing the transcriptional networks initiated by Pax4 and Arx in early committed beta- and alpha-cell, respectively. Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract <jats:italic>Arx<\/jats:italic> gene activity in early committed beta-cells.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-213x-11-52","type":"journal-article","created":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T01:36:58Z","timestamp":1314841018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin\/ghrelin co-expressing cell lineage"],"prefix":"10.1186","volume":"11","author":[{"given":"Simon","family":"Kordowich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Collombat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Mansouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palle","family":"Serup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,8,31]]},"reference":[{"key":"649_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/BF01228136","volume":"14","author":"TE Adrian","year":"1978","unstructured":"Adrian TE, Bloom SR, Hermansen K, Iversen J: Pancreatic polypeptide, glucagon and insulin secretion from the isolated perfused canine pancreas. 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