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XB-ART-39103
Development April 1, 2009; 136 (7): 1071-81.

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



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.

PubMed ID: 19224982
PMC ID: PMC2685928
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acta2 actl6a chrd.1 cpn1 dkk1 fn1 frzb frzb2 fzd3 kit lama1 mapk8 muc2 muc2l nrp1 pitx3 sfrp1 sfrp2 sfrp5 six1 tbx2 tuba4b vgll2 wif1 wnt2 wnt3a wnt4 wnt8a wnt8b
Antibodies: Lama1 Ab1 Lama1 Ab2
Morpholinos: frzb2 MO1

GEO Series: GSE13377: NCBI

Article Images: [+] show captions
References [+] :
Agathon, The molecular nature of the zebrafish tail organizer. 2003, Pubmed