Genetic patterning of the posterior neuropore region of curly tail mouse embryos: deficiency of Wnt5a expression.
The mouse mutant curly tail (ct) develops tail flexion defects and spina bifida as the result of delayed or failed closure of the posterior neuropore (PNP). With the aim of identifying genes involved in the chain of events resulting in defective neurulation, which can be detected at day 10.5 of development, we examined the expression patterns of a number of genes implicated in patterning of axial structures, mesoderm and neuroepithelium. The genes analyzed were Shh, HNF3alpha, HNF3beta, Brachyury, Hoxb1, Evx1, Fgf8, Wnt5a and Wnt5b. No differences could be detected between non-mutant embryos and ct/ct embryos with normal PNP size for any of these genes. Comparisons between ct/ct embryos with enlarged PNP and phenotypically normal ct/ct or nonmutant embryos showed differences only for Wnt5a. Expression of this gene was greatly reduced in the ventral caudal mesoderm and hindgut endoderm. Analysis of younger embryos revealed that prior to the stage at which embryos at risk of developing neural tube defects can be detected, the same proportion of ct/ct embryos shows reduced Wnt5a expression. The proportion of embryos showing reduced expression and almost undetectable expression of Wnt5a reflects the proportions of tail defects and spina bifida seen at later stages. We suggest that deficiency of Wnt5a signaling in the ventral caudal region tissues is an important component of the mechanism of development of the defects in affected curly tail mutant mice, and that it is causally related to decreased cell proliferation within the ventral caudal region. A possible relationship between decreased Wnt5a expression and reduced levels of heparan sulphate proteoglycan is discussed.
Department of Human Anatomy, University of Oxford, United Kingdom. gofflot@gene.ucl.ac.be
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Gofflot
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Hall
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Morriss-Kay
D000818:Animals; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D009154:Mutation; D009436:Neural Tube Defects / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013623:Tail / Q000196:embryology*; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein