EARLY DELETION OF NEUROMERES IN WNT-1(- -) MUTANT MICE - EVALUATION BY MORPHOLOGICAL AND MOLECULAR MARKERS/

The Wnt-1 gene is required for the development of midbrain and cerebel lum; previous work showed that knockout of Wnt-1 causes the loss of mo st molecular markers of these structures in early embryos and deletion of these structures by birth. However, neither the extent of early ne uronal defects nor any possible alterations in structures adjacent to presumptive midbrain and cerebellum were examined. By using a neuron-s pecific antibody and fluorescent axon tracers, we show that central an d peripheral neuronal development are altered in mutants during initia l axonogenesis on embryonic day 9.5. The absence of neuronal landmarks , including oculomotor and trochlear nerves and cerebellar plate, sugg ests that both mesencephalon and rhombomere 1 (r1) are deleted, with t he remaining neural tube fused to form a new border between the caudal most portion of the prosencephalon (prosomere 1, or p1) and r2. Centra l axons accurately traverse this novel border by forming normal longit udinal tracts into the rhombencephalon, implying that the cues that di rect these axons are aligned across neuromeres and are not affected by the deletion. The presence of intact p1 and r2 is further supported b y the retention of markers for these two neuromeres, including a marke r of p1, the Sim-2 gene, and an r2-specific lacZ transgene in mutant e mbryos. In addition, alterations in the Sim-2 expression domain in ven tral prosencephalon, rostral to p1, provide novel evidence for Wnt-1 f unction in this region. (C) 1996 Wiley-Liss, Inc.