{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:12:47Z","timestamp":1793945567111,"version":"4.8.0"},"reference-count":39,"publisher":"The Company of Biologists","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:p>The specification of the different mouse pancreatic endocrine subtypes is determined by the concerted activities of transcription factors. However, the molecular mechanisms regulating endocrine fate allocation remain unclear. In the present study, we uncover the molecular consequences of the simultaneous depletion of Arx and Pax4 activity during pancreas development. Our findings reveal a so far unrecognized essential role of the paired-box-encoding Pax4 gene. Specifically, in the combined absence of Arx and Pax4, an early-onset loss of mature \u03b1- and \u03b2-cells occurs in the endocrine pancreas, concomitantly with a virtually exclusive generation of somatostatin-producing cells. Furthermore, despite normal development of the PP-cells in the double-mutant embryos, an atypical expression of the pancreatic polypeptide (PP) hormone was observed in somatostatin-labelled cells after birth. Additional characterizations indicate that such an expression of PP was related to the onset of feeding, thereby unravelling an epigenetic control. Finally, our data provide evidence that both Arx and Pax4 act as transcriptional repressors that control the expression level of one another, thereby mediating proper endocrine fate allocation.<\/jats:p>","DOI":"10.1242\/dev.01870","type":"journal-article","created":{"date-parts":[[2005,6,2]],"date-time":"2005-06-02T00:25:37Z","timestamp":1117671937000},"page":"2969-2980","source":"Crossref","is-referenced-by-count":217,"title":["The simultaneous loss of<i>Arx<\/i>and<i>Pax4<\/i>genes promotes a somatostatin-producing cell fate specification at the expense of the \u03b1-and \u03b2-cell lineages in the mouse endocrine pancreas"],"prefix":"10.1242","volume":"132","author":[{"given":"Patrick","family":"Collombat","sequence":"first","affiliation":[{"name":"Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Hecksher-S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Hagedorn Research Institute, Department of Developmental Biology, Niels Steensensvej 6, DK-2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vania","family":"Broccoli","sequence":"additional","affiliation":[{"name":"DIBIT, San Raffaele Scientific Institute, Via Olgenittina 58, I-20132 Milano,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Krull","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ponte","sequence":"additional","affiliation":[{"name":"DIBIT, San Raffaele Scientific Institute, Via Olgenittina 58, I-20132 Milano,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabea","family":"Mundiger","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Smith","sequence":"additional","affiliation":[{"name":"Centre de Biologie du De\u0301veloppement, UMR-5547 CNRS-Universite\u0301 P. Sabatier, 118 Route de Narbonne, F-31062 Toulouse, Cedex 04, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gruss","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palle","family":"Serup","sequence":"additional","affiliation":[{"name":"Hagedorn Research Institute, Department of Developmental Biology, Niels Steensensvej 6, DK-2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Mansouri","sequence":"additional","affiliation":[{"name":"Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Am Fassberg, 37077 Go\u0308ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042604533973700_REF1","doi-asserted-by":"crossref","unstructured":"Adrian, T. 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