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 spi na bifida as the result of delayed or failed closure of the posterior neuropore (PNP). With the aim of identifying genes involved in the cha in 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, HNF3 alpha HNF3 bet a, Brachyury, Hoxb1 Evx1, Fgf8, Wnt5a and Wnf5b. No differences could be detected between non-mutant embryos and ct/ct embryos with normal P NP size for any of these genes. Comparisons between ct/ct embryos with enlarged PNP and phenotypically normal ct/ct or nonmutant embryos sho wed differences only for Wnt5a. Expression of this gene was greatly re duced 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 propo rtion of ct/ct embryos shows reduced Wnt5a expression. The proportion of embryos showing reduced expression and almost undetectable expressi on 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 me chanism of development of the defects in affected curly fail mutant mi ce, and that it is causally related to decreased cell proliferation wi thin the ventral caudal region. A possible relationship between decrea sed Wnt5a expression and reduced levels of heparan sulphate proteoglyc an is discussed.