Endodermal expression of Nkx6 genes depends differentially on Pdx1

TY - JOUR

T1 - Endodermal expression of Nkx6 genes depends differentially on Pdx1

AU - Pedersen, Jesper K

AU - Nelson, Shelley B

AU - Jørgensen, Mette Christine

AU - Henseleit, Korinna D

AU - Fujitani, Yoshio

AU - Wright, Chris V E

AU - Sander, Maike

AU - Serup, Palle

AU - Beta Cell Biology Consortium

PY - 2005/12/15

Y1 - 2005/12/15

N2 - Nkx family members are essential for normal development of many different tissues such as the heart, lungs, thyroid, prostate, and CNS. Here, we describe the endodermal expression pattern of three Nkx6 family genes of which two shows conserved expression in the early pancreatic epithelium. In chicken, Nkx6.1 expression is not restricted to the presumptive pancreatic area but is more broadly expressed in the endoderm. In mice, expression of Nkx6.1 is restricted to the pancreatic epithelium. In both mice and chicken, Nkx6.2 and Pdx1 are expressed in very similar domains, identifying Nkx6.2 as a novel marker of pancreas endoderm. Additionally, our results show that Nkx6.3 is expressed transiently in pancreatic endoderm in chicken but not mouse embryos. At later stages, Nkx6.3 is found in the caudal stomach and rostral duodenum in both species. Finally, we demonstrate that Pdx1 is required for Nkx6.1 but not Nkx6.2 expression in mice and that ectopic Pdx1 can induce Nkx6.1 but not Nkx6.2 or Nkx6.3 expression in anterior chicken endoderm. These results demonstrate that Nkx6.1 lies downstream of Pdx1 in a genetic pathway and that Pdx1 is required and sufficient for Nkx6.1 expression in the early foregut endoderm.

AB - Nkx family members are essential for normal development of many different tissues such as the heart, lungs, thyroid, prostate, and CNS. Here, we describe the endodermal expression pattern of three Nkx6 family genes of which two shows conserved expression in the early pancreatic epithelium. In chicken, Nkx6.1 expression is not restricted to the presumptive pancreatic area but is more broadly expressed in the endoderm. In mice, expression of Nkx6.1 is restricted to the pancreatic epithelium. In both mice and chicken, Nkx6.2 and Pdx1 are expressed in very similar domains, identifying Nkx6.2 as a novel marker of pancreas endoderm. Additionally, our results show that Nkx6.3 is expressed transiently in pancreatic endoderm in chicken but not mouse embryos. At later stages, Nkx6.3 is found in the caudal stomach and rostral duodenum in both species. Finally, we demonstrate that Pdx1 is required for Nkx6.1 but not Nkx6.2 expression in mice and that ectopic Pdx1 can induce Nkx6.1 but not Nkx6.2 or Nkx6.3 expression in anterior chicken endoderm. These results demonstrate that Nkx6.1 lies downstream of Pdx1 in a genetic pathway and that Pdx1 is required and sufficient for Nkx6.1 expression in the early foregut endoderm.

KW - Amino Acid Sequence

KW - Animals

KW - Chick Embryo

KW - Endoderm

KW - Gene Expression Regulation, Developmental

KW - Homeodomain Proteins

KW - Mice

KW - Mice, Mutant Strains

KW - Molecular Sequence Data

KW - Pancreas

KW - Phylogeny

KW - Sequence Homology, Amino Acid

KW - Trans-Activators

KW - Transcription Factors

U2 - 10.1016/j.ydbio.2005.10.001

DO - 10.1016/j.ydbio.2005.10.001

M3 - Journal article

C2 - 16297379

SN - 0012-1606

VL - 288

SP - 487

EP - 501

JO - Developmental Biology

JF - Developmental Biology

IS - 2

ER -