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 cerebellum; previous work showed that knockout of Wnt-1 causes the loss of most molecular markers of these structures in early embryos and deletion of these structures by birth. However, neither the extent of early neuronal defects nor any possible alterations in structures adjacent to presumptive midbrain and cerebellum were examined. By using a neuron-specific antibody and fluorescent axon tracers, we show that central and peripheral neuronal development are altered in mutants during initial axonogenesis on embryonic day 9.5. The absence of neuronal landmarks, including oculomotor and trochlear nerves and cerebellar plate, suggests that both mesencephalon and rhombomere 1 (r1) are delected, with the remaining neural tube fused to form a new border between the caudalmost portion of the prosencephalon (prosomere 1, or p1) and r2. Central axons accurately traverse this novel border by forming normal longitudinal tracts into the rhombencephalon, implying that the cues that direct these axons are aligned across neuromeres and are not affected by the delection. The presence of intact p1 and r2 is further supported by the retention of markers for these two neuromers, including a marker of p1, the Sim-2 gene, and an r2-specific lacZ transgene in mutant embryos. In addition, alterations in the Sim-2 expression domain in ventral prosencephalon, rostral to p1, provide novel evidence for Wnt-1 function in this region.
Mastick
G S
GS
Department of Biology, University of Michigan, Ann Arbor 48109,USA. grants@umich.edu
Fan
C M
CM
Tessier-Lavigne
M
M
Serbedzija
G N
GN
McMahon
A P
AP
Easter
S S
SS
D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D001921:Brain / Q000033:anatomy & histology*; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009474:Neurons / Q000648:ultrastructure*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013997:Time Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins