DISPERSION PATTERNS OF RETINAL NEUROBLASTS

这项研究计划将定义神经母细胞

This research proposal will define the ways in which neuroblasts of distinct laminar and functional fate disperse within the retina. Transgenic mice carrying the bacterial lacZ gene inserted on the X chromosome will be used, and the natural, random phenomenon of X inactivation in hemizygous females will restrict expression of the transgene to half of all retinal neurons. Since X inactivation occurs before any retinal neuroblasts have been born, and because progeny inherit the X-active status of their progenitors, this approach permits the marking of large numbers of retinal clones. Chimeric mice, formed by combining lacZ-expressing embryonic cells with wild-type embryos, will also be used to label small numbers of retinal clones in order to confirm the results from the X-inactivation transgenic mosaic mice. Retinae from both transgenic and chimeric adult mice show a conspicuous columnar arrangement of such clones of cells, but also reveal that distinct types of retinal cell do not respect this columnar segregation. The distributions of the clonally related cells suggest that the dispersion pattern of a neuroblast from the germinal zone of the developing retina can include a tangential as well as a radial component, but that the expression of the tangential component is confined to distinct subsets of retinal neuroblast. The present investigation will examine two hypotheses for this tangential dispersion. First, is tangential dispersion due to a passive displacement of these cells as the remainder of the retinal cells proliferate? And second, is the tangential dispersion due to an active displacement of the postmitotic neuroblasts, playing a role in the establishment of the orderly spacing between neurons of particular classes? Adult and developing retinae will be examined, in which cohorts of retinal cells sharing common birthdates will have been labelled during embryogenesis. Distinct types of retinal cells will b identified using immunocytochemistry to correlate phenotype and intercellular spacing with extent of tangential dispersion. These studies will clarify the mechanisms underlying the creation of the mature retinal architecture.