Zebrafish mutants identify an essential role for laminins in notochord formation

Michael J. Parsons, Steven M. Pollard, Leonor Saúde, Benjamin Feldman, Pedro Coutinho, Elizabeth M.A. Hirst, Derek L. Stemple

Research output: Contribution to journalReview articlepeer-review

191 Scopus citations


Basement membranes are thought to be essential for organ formation, providing the scaffold on which individual cells organize to form complex tissues. Laminins are integral components of basement membranes. To understand the development of a simple vertebrate organ, we have used positional cloning to characterize grumpy and sleepy, two zebrafish loci known to control notochord formation, and find that they encode laminin β1 and laminin γ1, respectively. Removal of either chain results in the dramatic loss of laminin 1 staining throughout the embryo and prevents formation of the basement membrane surrounding the notochord. Notochord cells fail to differentiate and many die by apoptosis. By transplantation, we demonstrate that, for both grumpy and sleepy, notochord differentiation can be rescued by exogenous sources of the missing laminin chain, although notochordal sources are also sufficient for rescue. These results demonstrate a clear in vivo requirement for laminin β1 and laminin γ1 in the formation of a specific vertebrate organ and show that laminin or the laminin-dependent basement membrane is essential for the differentiation of chordamesoderm to notochord.

Original languageEnglish (US)
Pages (from-to)3137-3146
Number of pages10
Issue number13
StatePublished - Aug 23 2002


  • Basement membrane
  • Differentiation
  • Laminin
  • Notochord
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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