NDLI: Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors

Content Provider	PubMed Central
Author	Vas, Matias G. De Kopp, Janel L. Heliot, Claire Sander, Maike Silvia, Cereghini Haumaitre, Cécile
Copyright Year	2015
Abstract	Heterozygous mutations in the human HNF1B gene are associated with maturity-onset diabetes of the young type 5 (MODY5) and pancreas hypoplasia. In mouse, Hnf1b heterozygous mutants do not exhibit any phenotype, whereas the homozygous deletion in the entire epiblast leads to pancreas agenesis associated with abnormal gut regionalization. Here, we examine the specific role of Hnf1b during pancreas development, using constitutive and inducible conditional inactivation approaches at key developmental stages. Hnf1b early deletion leads to a reduced pool of pancreatic multipotent progenitor cells (MPCs) due to decreased proliferation and increased apoptosis. Lack of Hnf1b either during the first or the secondary transitions is associated with cystic ducts. Ductal cells exhibit aberrant polarity and decreased expression of several cystic disease genes, some of which we identified as novel Hnf1b targets. Notably, we show that Glis3, a transcription factor involved in duct morphogenesis and endocrine cell development, is downstream Hnf1b. In addition, a loss and abnormal differentiation of acinar cells are observed. Strikingly, inactivation of Hnf1b at different time points results in the absence of Ngn3+ endocrine precursors throughout embryogenesis. We further show that Hnf1b occupies novel Ngn3 putative regulatory sequences in vivo. Thus, Hnf1b plays a crucial role in the regulatory networks that control pancreatic MPC expansion, acinar cell identity, duct morphogenesis and generation of endocrine precursors. Our results uncover an unappreciated requirement of Hnf1b in endocrine cell specification and suggest a mechanistic explanation of diabetes onset in individuals with MODY5.
Related Links	http://dx.doi.org/10.1242/dev.110759
Ending Page	882
Page Count	12
Starting Page	871
File Format	PDF
ISSN	09501991
e-ISSN	14779129
Journal	Development (Cambridge, England)
Issue Number	5
Volume Number	142
Language	English
Publisher	The Company of Biologists
Publisher Date	2015-03-01
Access Restriction	Open
Rights Holder	The Company of Biologists
Subject Keyword	Developmental Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Hnf1b controls pancreas morphogenesis and the generation of $Ngn3^{+}$ endocrine progenitors

The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

NGN3 oscillatory expression controls the timing of human pancreatic endocrine differentiation

Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas

Biphasic Ngn3 expression in the developing pancreas

Transcription Factor Hepatocyte Nuclear Factor 6 Regulates Pancreatic Endocrine Cell Differentiation and Controls Expression of the Proendocrine Gene ngn3

Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors

Similar Documents

Hnf1b controls pancreas morphogenesis and the generation of $Ngn3^{+}$ endocrine progenitors

The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

NGN3 oscillatory expression controls the timing of human pancreatic endocrine differentiation

Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas

Biphasic Ngn3 expression in the developing pancreas

Transcription Factor Hepatocyte Nuclear Factor 6 Regulates Pancreatic Endocrine Cell Differentiation and Controls Expression of the Proendocrine Gene ngn3

Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors