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
  • Organogenesis/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Matrix Metalloproteinases/metabolism
  • Zebrafish/embryology*
  • Extracellular Matrix/metabolism*
  • Cell Differentiation/physiology
  • Laminin/metabolism
  • Cell Lineage/physiology
  • Animals, Genetically Modified
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Gastrointestinal Tract/cytology
  • Gastrointestinal Tract/embryology*
  • Gastrointestinal Tract/metabolism*
  • Cell Movement/physiology
  • Animals
  • Mesoderm/cytology
  • Mesoderm/metabolism
  • Body Patterning/physiology
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Transgenes/genetics
(all 23)
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
Figure Gallery (11 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment: pharmaceuticalPrim-15
fr13Tg; pd24Tgheat shockPrim-15
hand2c99/+controlPrim-15
hand2c99/+chemical treatment: pharmaceuticalPrim-15
hand2c99/+ + MO4-mmp14astandard conditionsPrim-15
hand2c99/c99standard conditionsPrim-15
hand2c99/c99standard conditionsPrim-15
hand2c99/c99standard conditionsPrim-15
hand2c99/c99standard conditionsLong-pec
hand2c99/c99standard conditionsLong-pec
1 - 10 of 23
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c99
    		Insertion
    fr13TgTransgenic Insertion
      pd24TgTransgenic Insertion
        s40
          		Unknown
          s804
            		Point Mutation
            w30TgTransgenic Insertion
              1 - 6 of 6
              Show
              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              mmp14aMO4-mmp14aMRPHLNO
              spawMO1-spawMRPHLNO
              1 - 2 of 2
              Show
              Fish
              Fish
              fr13Tg
              fr13Tg; pd24Tg
              hand2c99/c99
              hand2c99/c99; pd24Tg
              hand2c99/+
              hand2c99/+
              hand2c99/+ + MO4-mmp14a
              hand2s40/s40
              hand2s40/s40; pd24Tg
              lamb1as804/s804
              1 - 10 of 16
              Show
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GFPEFGGFP
              1 - 2 of 2
              Show
              Mapping
              No data available
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              Citation
              Yin, C., Kikuchi, K., Hochgreb, T., Poss, K.D., and Stainier, D.Y. (2010) Hand2 Regulates Extracellular Matrix Remodeling Essential for Gut-Looping Morphogenesis in Zebrafish. Developmental Cell. 18(6):973-984.