TY - JOUR
T1 - Gata6 is an important regulator of mouse pancreas development
AU - Decker, Kimberly
AU - Goldman, Devorah C.
AU - L. Grasch, Catherine
AU - Sussel, Lori
N1 - Funding Information:
We thank J. Jensen (Barbara Davis Center, UCHSC) and K. Artinger (UCHSC) for the generous gifts of the Pdx1 promoter vector and pCS2-EnR vector, respectively. We thank D. Srivastava (UCSF) and C. Glembotski (UCSD) for Gata-reporter vectors. Special thanks to Keith Anderson for assistance with the luciferase assays. We thank Lee Niswander, Kristin Artinger and members of the Sussel lab for critical reading of the manuscript. This research was supported by the NIH NIDDK (L.S.) and a Juvenile Diabetes Foundation Postdoctoral fellowship (D.G.). Additional support was provided by the University of Colorado Cancer Center Transgenic/Knockout Core and the Diabetes and Endocrinology Research Center (NIH P30 DK57516).
PY - 2006/10/15
Y1 - 2006/10/15
N2 - Gata4, Gata5, and Gata6 represent a subfamily of zinc-finger transcriptional regulators that are important in the development and differentiation of numerous tissues, including many endodermally-derived organs. We demonstrate that Gata4 and Gata6 have overlapping expression patterns in the early pancreatic epithelium. Later, Gata4 becomes restricted to exocrine tissue and Gata6 becomes restricted to a subset of endocrine cells. In addition, we show Gata6, but not Gata4, physically interacts with Nkx2.2, an essential islet transcription factor. To begin determining the roles that Gata4 and Gata6 play during pancreatic development, we expressed Gata4-Engrailed and Gata6-Engrailed dominant repressor fusion proteins in the pancreatic epithelium and in the islet. At e17.5, transgenic Gata6-Engrailed embryos exhibit two distinct phenotypes: a complete absence of pancreas or a reduction in pancreatic tissue. In the embryos that do form pancreas, there is a significant reduction of all pancreatic cell types, with the few differentiated endocrine cells clustered within, or in close proximity to, enlarged ductal structures. Conversely, the majority of transgenic Gata4-Engrailed embryos do not have a pancreatic phenotype. This study suggests that Gata6 is an important regulator of pancreas specification.
AB - Gata4, Gata5, and Gata6 represent a subfamily of zinc-finger transcriptional regulators that are important in the development and differentiation of numerous tissues, including many endodermally-derived organs. We demonstrate that Gata4 and Gata6 have overlapping expression patterns in the early pancreatic epithelium. Later, Gata4 becomes restricted to exocrine tissue and Gata6 becomes restricted to a subset of endocrine cells. In addition, we show Gata6, but not Gata4, physically interacts with Nkx2.2, an essential islet transcription factor. To begin determining the roles that Gata4 and Gata6 play during pancreatic development, we expressed Gata4-Engrailed and Gata6-Engrailed dominant repressor fusion proteins in the pancreatic epithelium and in the islet. At e17.5, transgenic Gata6-Engrailed embryos exhibit two distinct phenotypes: a complete absence of pancreas or a reduction in pancreatic tissue. In the embryos that do form pancreas, there is a significant reduction of all pancreatic cell types, with the few differentiated endocrine cells clustered within, or in close proximity to, enlarged ductal structures. Conversely, the majority of transgenic Gata4-Engrailed embryos do not have a pancreatic phenotype. This study suggests that Gata6 is an important regulator of pancreas specification.
KW - Gata4
KW - Gata6
KW - Islet
KW - Pancreas development
UR - http://www.scopus.com/inward/record.url?scp=33748963738&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748963738&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2006.06.046
DO - 10.1016/j.ydbio.2006.06.046
M3 - Article
C2 - 16887115
AN - SCOPUS:33748963738
SN - 0012-1606
VL - 298
SP - 415
EP - 429
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -