ZFIN ID: ZDB-PUB-070122-35
Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell development in zebrafish
Song, J., Kim, H.J., Gong, Z., Liu, N.A., and Lin, S.
Date: 2007
Source: Developmental Biology   303(2): 561-575 (Journal)
Registered Authors: Gong, Zhiyuan, Lin, Shuo, Liu, Ningai, Song, Jianbo
Keywords: Zebrafish, Pancreas development, Fgf, RA, Bmp, vhnf1
MeSH Terms:
  • Animals
  • Base Sequence
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • Epistasis, Genetic
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism*
  • Gene Expression Regulation, Developmental/drug effects
  • Hepatocyte Nuclear Factor 1-beta/genetics
  • Hepatocyte Nuclear Factor 1-beta/metabolism*
  • Insulin/genetics
  • Insulin/metabolism
  • Insulin-Secreting Cells/cytology*
  • Insulin-Secreting Cells/drug effects
  • Insulin-Secreting Cells/metabolism*
  • Models, Biological
  • Oligodeoxyribonucleotides, Antisense/genetics
  • Point Mutation
  • Signal Transduction
  • Tretinoin/metabolism*
  • Tretinoin/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 17217944 Full text @ Dev. Biol.
Bmp, Fgf, and retinoic acid (RA) signals have been implicated as regulators of pancreas development. However, the integration of these signaling pathways in vivo is not fully understood. Variant hnf1 (Vhnf1) is a transcription factor involved in pancreas, liver, and kidney development and its mutation in zebrafish causes underdeveloped pancreas and liver. We investigated the signaling pathways that regulate vhnf1 expression during pancreas development. First, we showed that Bmp activity is required for vhnf1 expression in the endoderm. In chordin (a Bmp antagonist) morpholino (MO)-injected embryos, vhnf1 expression in endoderm and in endocrine beta cells is expanded. On the other hand, in alk8 (a type I TGFbeta receptor) MO-injected embryos, vhnf1 expression in the endoderm is significantly reduced. Second, we showed that Fgf signaling participates in regulation of pancreas development through the vhnf1 pathway. Third, we demonstrated that RA fails to rescue reduction of insulin expression in vhnf1 mutants, whereas overexpression of vhnf1 restores insulin expression that is repressed by treatment with a RA receptor inhibitor. And finally, we revealed that both Bmp and Fgf signals act genetically upstream of RA in directing pancreas development. Taken together, our data establish that vhnf1 acts downstream of the signaling pathways of RA, Bmp, and Fgf to regulate pancreas development in zebrafish.