ZFIN ID: ZDB-PUB-100719-51
Hand2 Regulates Extracellular Matrix Remodeling Essential for Gut-Looping Morphogenesis in Zebrafish
Yin, C., Kikuchi, K., Hochgreb, T., Poss, K.D., and Stainier, D.Y.
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:
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Body Patterning/physiology
  • Cell Differentiation/physiology
  • Cell Lineage/physiology
  • Cell Movement/physiology
  • Extracellular Matrix/metabolism*
  • Gastrointestinal Tract/cytology
  • Gastrointestinal Tract/embryology*
  • Gastrointestinal Tract/metabolism*
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Laminin/metabolism
  • Matrix Metalloproteinases/metabolism
  • Mesoderm/cytology
  • Mesoderm/metabolism
  • Organogenesis/physiology*
  • Transgenes/genetics
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 20627079 Full text @ Dev. Cell
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.