PUBLICATION

Hand2 Regulates Extracellular Matrix Remodeling Essential for Gut-Looping Morphogenesis in Zebrafish

Authors
Yin, C., Kikuchi, K., Hochgreb, T., Poss, K.D., and Stainier, D.Y.
ID
ZDB-PUB-100719-51
Date
2010
Source
Developmental Cell   18(6): 973-984 (Journal)
Registered Authors
Hochgreb, Tatiana, Kikuchi, Kazu, Poss, Kenneth D., Stainier, Didier, Yin, Chunyue
Keywords
none
MeSH Terms
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Laminin/metabolism
  • Transgenes/genetics
  • Cell Movement/physiology
  • Zebrafish/embryology*
  • Matrix Metalloproteinases/metabolism
  • Cell Differentiation/physiology
  • Mesoderm/cytology
  • Mesoderm/metabolism
  • Organogenesis/physiology*
  • Gastrointestinal Tract/cytology
  • Gastrointestinal Tract/embryology*
  • Gastrointestinal Tract/metabolism*
  • Extracellular Matrix/metabolism*
  • Cell Lineage/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Body Patterning/physiology
PubMed
20627079 Full text @ Dev. Cell
Abstract
Extracellular matrix (ECM) remodeling is critical for organogenesis, yet its molecular regulation is poorly understood. In zebrafish, asymmetric migration of the epithelial lateral plate mesoderm (LPM) displaces the gut leftward, allowing correct placement of the liver and pancreas. To observe LPM migration at cellular resolution, we transgenically expressed EGFP under the control of the regulatory sequences of the bHLH transcription factor gene hand2. We found that laminin is distributed along the LPM/gut boundary during gut looping, and that it appears to become diminished by the migrating hand2-expressing cells. Laminin diminishment is necessary for LPM migration and is dependent on matrix metalloproteinase (MMP) activity. Loss of Hand2 function causes reduced MMP activity and prolonged laminin deposition at the LPM/gut boundary, leading to failed asymmetric LPM migration and gut looping. Our study reveals an unexpected role for Hand2, a key regulator of cell specification and differentiation, in modulating ECM remodeling during organogenesis.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping