The Wnt antagonists Frzb-1 and Crescent locally regulate basement membrane dissolution in the developing primary mouth

Development. 2009 Apr;136(7):1071-81. doi: 10.1242/dev.032912. Epub 2009 Feb 18.

Abstract

The primary mouth forms from ectoderm and endoderm at the extreme anterior of the embryo, a conserved mesoderm-free region. In Xenopus, a very early step in primary mouth formation is loss of the basement membrane between the ectoderm and endoderm. In an unbiased microarray screen, we defined genes encoding the sFRPs Frzb-1 and Crescent as transiently and locally expressed in the primary mouth anlage. Using antisense oligonucleotides and ;face transplants', we show that frzb-1 and crescent expression is specifically required in the primary mouth region at the time this organ begins to form. Several assays indicate that Frzb-1 and Crescent modulate primary mouth formation by suppressing Wnt signaling, which is likely to be mediated by beta-catenin. First, a similar phenotype (no primary mouth) is seen after loss of Frzb-1/Crescent function to that seen after temporally and spatially restricted overexpression of Wnt-8. Second, overexpression of either Frzb-1 or Dkk-1 results in an enlarged primary mouth anlage. Third, overexpression of Dkk-1 can restore a primary mouth to embryos in which Frzb-1/Crescent expression has been inhibited. We show that Frzb-1/Crescent function locally promotes basement membrane dissolution in the primary mouth primordium. Consistently, Frzb-1 overexpression decreases RNA levels of the essential basement membrane genes fibronectin and laminin, whereas Wnt-8 overexpression increases the levels of these RNAs. These data are the first to connect Wnt signaling and basement membrane integrity during primary mouth development, and suggest a general paradigm for the regulation of basement membrane remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Basement Membrane / embryology
  • Gene Expression Regulation, Developmental
  • Glycoproteins / genetics
  • Glycoproteins / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Models, Biological
  • Mouth / embryology*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • RNA / genetics
  • RNA / metabolism
  • Signal Transduction
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / genetics
  • Wnt Proteins / physiology
  • Xenopus Proteins / antagonists & inhibitors
  • Xenopus Proteins / genetics
  • Xenopus Proteins / physiology*
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / physiology

Substances

  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • WD repeat containing planar cell polarity effector
  • Wnt Proteins
  • Xenopus Proteins
  • frzb2 protein, Xenopus
  • wnt8a protein, Xenopus
  • RNA