Targeted disruption of mouse Dach1 results in postnatal lethality.

Mouse Dach1 is a nuclear factor that is expressed during development in restricted areas of the central nervous system, neural crest, and limb buds. Its Drosophila homologue dachshund plays a role in differentiation of the eye imaginal disc, in leg morphogenesis, and in controlling neural differentiation in the mushroom bodies of the insect brain. Mouse Dach1 null homozygous survive pregnancy but become cyanotic after birth and subsequently die within 24 hr. In this report, the brain of Dach1 mutants was analyzed. Examination of mRNA expression of the central neuropeptides oxytocin, vasopressin, thyrotropin-releasing hormone, growth hormone releasing hormone, and somatostatin revealed no difference between wild-type and mutant newborn brains. Furthermore, no significant difference in cell proliferation as well as in the distribution of neurons, glia, radial glia, and neuronal progenitors was detected in the developing forebrain. Dach1-positive cells, which were visualized with Enhanced Green Fluorescent Protein (EGFP), show similar distribution and axonal projections in the cortex and hippocampus in mutants and wild-type controls. Neural stem cells derived from mutant and wild-type newborn brains display similar growth kinetics when cultivated in vitro.