Hand2 regulates extracellular matrix remodeling essential for gut-looping morphogenesis in zebrafish.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yin, C; Kikuchi, K; Hochgreb, T; Poss, KD; Stainier, DYR

Published Date

  • June 15, 2010

Published In

Volume / Issue

  • 18 / 6

Start / End Page

  • 973 - 984

PubMed ID

  • 20627079

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2010.05.009

Language

  • eng

Conference Location

  • United States