| We investigate fundamental processes that direct mammalian embryonic development. To this end we take advantage of the mouse as an in vivo model system, utilising two different genetic approaches. Forward genetics We have initiated a forward screen for developmental mutations. This involves backcrossing of mutagen-treated mice, followed by identification of mutant lines on the basis of observed malformed embryos. This approach has allowed identification of a number of new mutants that we are currently analysing and mapping (collaboration with the Cuppen group in the Institute). In these mutants we see neural tube closure defects (fig. 1), cardiac malformations (fig. 2) and early gastrulation defects. Reverse genetics Using gene targeting technology we have inactivated members of the aristaless' family of paired-type homeobox genes, and characterised the resulting skeletal (fig. 5 and 6) and cardiac defects. |