Cargando…

Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans

Insulin from the β-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor Neurogenin3 initiates the differentiation of the β-cells and other islet cell types from pan...

Descripción completa

Detalles Bibliográficos
Autores principales: Smith, Stuart B., Qu, Hui-Qi, Taleb, Nadine, Kishimoto, Nina, Scheel, David W., Lu, Yang, Patch, Ann-Marie, Grabs, Rosemary, Wang, Juehu, Lynn, Francis C., Miyatsuka, Takeshi, Mitchell, John, Seerke, Rina, Désir, Julie, Eijnden, Serge Vanden, Abramowicz, Marc, Kacet, Nadine, Weill, Jacques, Renard, Marie-Éve, Gentile, Mattia, Hansen, Inger, Dewar, Ken, Hattersley, Andrew T., Wang, Rennian, Wilson, Maria E., Johnson, Jeffrey D., Polychronakos, Constantin, German, Michael S.
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896718/
https://www.ncbi.nlm.nih.gov/pubmed/20148032
http://dx.doi.org/10.1038/nature08748
_version_ 1782183387371405312
author Smith, Stuart B.
Qu, Hui-Qi
Taleb, Nadine
Kishimoto, Nina
Scheel, David W.
Lu, Yang
Patch, Ann-Marie
Grabs, Rosemary
Wang, Juehu
Lynn, Francis C.
Miyatsuka, Takeshi
Mitchell, John
Seerke, Rina
Désir, Julie
Eijnden, Serge Vanden
Abramowicz, Marc
Kacet, Nadine
Weill, Jacques
Renard, Marie-Éve
Gentile, Mattia
Hansen, Inger
Dewar, Ken
Hattersley, Andrew T.
Wang, Rennian
Wilson, Maria E.
Johnson, Jeffrey D.
Polychronakos, Constantin
German, Michael S.
author_facet Smith, Stuart B.
Qu, Hui-Qi
Taleb, Nadine
Kishimoto, Nina
Scheel, David W.
Lu, Yang
Patch, Ann-Marie
Grabs, Rosemary
Wang, Juehu
Lynn, Francis C.
Miyatsuka, Takeshi
Mitchell, John
Seerke, Rina
Désir, Julie
Eijnden, Serge Vanden
Abramowicz, Marc
Kacet, Nadine
Weill, Jacques
Renard, Marie-Éve
Gentile, Mattia
Hansen, Inger
Dewar, Ken
Hattersley, Andrew T.
Wang, Rennian
Wilson, Maria E.
Johnson, Jeffrey D.
Polychronakos, Constantin
German, Michael S.
author_sort Smith, Stuart B.
collection PubMed
description Insulin from the β-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor Neurogenin3 initiates the differentiation of the β-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurogenin3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate β-cells for patients with diabetes.
format Text
id pubmed-2896718
institution National Center for Biotechnology Information
language English
publishDate 2010
record_format MEDLINE/PubMed
spelling pubmed-28967182010-08-11 Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans Smith, Stuart B. Qu, Hui-Qi Taleb, Nadine Kishimoto, Nina Scheel, David W. Lu, Yang Patch, Ann-Marie Grabs, Rosemary Wang, Juehu Lynn, Francis C. Miyatsuka, Takeshi Mitchell, John Seerke, Rina Désir, Julie Eijnden, Serge Vanden Abramowicz, Marc Kacet, Nadine Weill, Jacques Renard, Marie-Éve Gentile, Mattia Hansen, Inger Dewar, Ken Hattersley, Andrew T. Wang, Rennian Wilson, Maria E. Johnson, Jeffrey D. Polychronakos, Constantin German, Michael S. Nature Article Insulin from the β-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor Neurogenin3 initiates the differentiation of the β-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurogenin3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate β-cells for patients with diabetes. 2010-02-11 /pmc/articles/PMC2896718/ /pubmed/20148032 http://dx.doi.org/10.1038/nature08748 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Smith, Stuart B.
Qu, Hui-Qi
Taleb, Nadine
Kishimoto, Nina
Scheel, David W.
Lu, Yang
Patch, Ann-Marie
Grabs, Rosemary
Wang, Juehu
Lynn, Francis C.
Miyatsuka, Takeshi
Mitchell, John
Seerke, Rina
Désir, Julie
Eijnden, Serge Vanden
Abramowicz, Marc
Kacet, Nadine
Weill, Jacques
Renard, Marie-Éve
Gentile, Mattia
Hansen, Inger
Dewar, Ken
Hattersley, Andrew T.
Wang, Rennian
Wilson, Maria E.
Johnson, Jeffrey D.
Polychronakos, Constantin
German, Michael S.
Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans
title Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans
title_full Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans
title_fullStr Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans
title_full_unstemmed Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans
title_short Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans
title_sort rfx6 directs islet formation and insulin production in mice and humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896718/
https://www.ncbi.nlm.nih.gov/pubmed/20148032
http://dx.doi.org/10.1038/nature08748
work_keys_str_mv AT smithstuartb rfx6directsisletformationandinsulinproductioninmiceandhumans
AT quhuiqi rfx6directsisletformationandinsulinproductioninmiceandhumans
AT talebnadine rfx6directsisletformationandinsulinproductioninmiceandhumans
AT kishimotonina rfx6directsisletformationandinsulinproductioninmiceandhumans
AT scheeldavidw rfx6directsisletformationandinsulinproductioninmiceandhumans
AT luyang rfx6directsisletformationandinsulinproductioninmiceandhumans
AT patchannmarie rfx6directsisletformationandinsulinproductioninmiceandhumans
AT grabsrosemary rfx6directsisletformationandinsulinproductioninmiceandhumans
AT wangjuehu rfx6directsisletformationandinsulinproductioninmiceandhumans
AT lynnfrancisc rfx6directsisletformationandinsulinproductioninmiceandhumans
AT miyatsukatakeshi rfx6directsisletformationandinsulinproductioninmiceandhumans
AT mitchelljohn rfx6directsisletformationandinsulinproductioninmiceandhumans
AT seerkerina rfx6directsisletformationandinsulinproductioninmiceandhumans
AT desirjulie rfx6directsisletformationandinsulinproductioninmiceandhumans
AT eijndensergevanden rfx6directsisletformationandinsulinproductioninmiceandhumans
AT abramowiczmarc rfx6directsisletformationandinsulinproductioninmiceandhumans
AT kacetnadine rfx6directsisletformationandinsulinproductioninmiceandhumans
AT weilljacques rfx6directsisletformationandinsulinproductioninmiceandhumans
AT renardmarieeve rfx6directsisletformationandinsulinproductioninmiceandhumans
AT gentilemattia rfx6directsisletformationandinsulinproductioninmiceandhumans
AT hanseninger rfx6directsisletformationandinsulinproductioninmiceandhumans
AT dewarken rfx6directsisletformationandinsulinproductioninmiceandhumans
AT hattersleyandrewt rfx6directsisletformationandinsulinproductioninmiceandhumans
AT wangrennian rfx6directsisletformationandinsulinproductioninmiceandhumans
AT wilsonmariae rfx6directsisletformationandinsulinproductioninmiceandhumans
AT johnsonjeffreyd rfx6directsisletformationandinsulinproductioninmiceandhumans
AT polychronakosconstantin rfx6directsisletformationandinsulinproductioninmiceandhumans
AT germanmichaels rfx6directsisletformationandinsulinproductioninmiceandhumans