000130614 001__ 130614
000130614 005__ 20240126184245.0
000130614 0247_ $$2doi$$a10.1210/en.2016-1745
000130614 0248_ $$2sideral$$a136577
000130614 037__ $$aART-2016-136577
000130614 041__ $$aeng
000130614 100__ $$aArregi, Igor
000130614 245__ $$aRetinol Dehydrogenase-10 Regulates Pancreas Organogenesis and Endocrine Cell Differentiation via Paracrine Retinoic Acid Signaling
000130614 260__ $$c2016
000130614 5203_ $$aVitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here, we show that retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme. Rdh10 null mutant mouse embryos exhibited dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Conditional disruption of Rdh10 from the endoderm caused increased mortality, reduced body weight, and lowered blood glucose levels after birth. Endodermal Rdh10 deficiency led to a smaller dorsal pancreas with a reduced density of early glucagon+ and insulin+ cells. During the secondary transition, the reduction of Neurogenin3+ endocrine progenitors in the mutant dorsal pancreas accounted for fewer α- and β-cells. Changes in the expression of α- and β-cell-specific transcription factors indicated that Rdh10 might also participate in the terminal differentiation of endocrine cells. Together, our results highlight the importance of both mesenchymal and epithelial Rdh10 for pancreogenesis and the first wave of endocrine cell differentiation. We further propose a model in which the Rdh10-expressing exocrine tissue acts as an essential source of RA signals in the second wave of endocrine cell differentiation.
000130614 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000130614 590__ $$a4.286$$b2016
000130614 591__ $$aENDOCRINOLOGY & METABOLISM$$b29 / 136 = 0.213$$c2016$$dQ1$$eT1
000130614 592__ $$a2.174$$b2016
000130614 593__ $$aEndocrinology$$c2016$$dQ1
000130614 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000130614 700__ $$0(orcid)0000-0002-0606-0763$$aCliment, Maria$$uUniversidad de Zaragoza
000130614 700__ $$aIliev, Dobromir
000130614 700__ $$aStrasser, Jürgen
000130614 700__ $$aGouignard, Nadège
000130614 700__ $$aJohansson, Jenny K.
000130614 700__ $$aSingh, Tania
000130614 700__ $$aMazur, Magdalena
000130614 700__ $$aSemb, Henrik
000130614 700__ $$aArtner, Isabella
000130614 700__ $$aMinichiello, Liliana
000130614 700__ $$aPera, Edgar M.
000130614 7102_ $$11001$$2025$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Anatom.Anatom.Patológ.Com
000130614 773__ $$g157, 12 (2016), 4615-4631$$pEndocrinology$$tENDOCRINOLOGY$$x0013-7227
000130614 787__ $$tRetinol Dehydrogenase-10 Regulates Pancreas Organogenesis and Endocrine Cell Differentiation via Paracrine Retinoic Acid Signaling$$w10.1210/en.2016-1745
000130614 8564_ $$s5469187$$uhttps://zaguan.unizar.es/record/130614/files/texto_completo.pdf$$yPostprint
000130614 8564_ $$s2468290$$uhttps://zaguan.unizar.es/record/130614/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000130614 909CO $$ooai:zaguan.unizar.es:130614$$particulos$$pdriver
000130614 951__ $$a2024-01-26-18:14:26
000130614 980__ $$aARTICLE