Programmed cell death and central nervous system (CNS) midline function in Drosophila embryonic development
Abstract (Summary)As an excellent organism for genetic study and with the many useful genetic manipulation tools developed in the past two decades, Drosophila melanogaster is an important model organism that has been utilized to understand the genetic regulation of various developmental processes. Here, we focus on the development of the Drosophila CNS midline cells to pursue a long term goal to understand (1) the regulation of programmed cell death during nervous system development and (2) the interaction between nervous system and the mesoderm structures during early embryonic development. Programmed cell death is an essential part of the development of the nervous system for vertebrate and invertebrate animals (reviewed by Oppenheim 1991). In the Drosophila CNS midline, about 70% of the glia cells die during a critical period. We found that the elimination of unwanted midline cells during embryonic nervous system development is a very well coordinated process, which ensures that specific number of midline glia survive. The others are relocated and executed by proteolytic cascade, followed by engulfment and further degradation by macrophages. We observed that three cell death regulatory genes (rpr, hid and grim) in the 75C1,2 region of the 3rd chromosome are all expressed in midline cells that are chosen to be executed. Using several mutants and genetic deficiencies, we found that in order for the appropriate number of midline cells to be eliminated, the functions of multiple genes in the 75C1,2 region are required. To further understand this cell death process, we targeted the expression of rpr and/or hid to midline cells. We found that the two genes show synergism in inducing ectopic cell death, further suggesting that they may functionally interact to regulate the proper cell death pattern. Inside the embryo, the development of the nervous system is not a isolated process. The developing nerve cells interact with the mesoderm during early embryonic development. We found that the CNS midline cells are required for the differentiation of a specific group of mesoderm cells, the dorsal median cell. The well conserved epidermal growth factor (EGF) signaling pathway is at least partially responsible for this CNS midline regulation of mesoderm cell development. In addition, we found that the proper anterior/posterior location of the dorsal median cells depends on the function of wingless or patched segmental polarity gene, and that these two genes might act through regulating the spatial differentiation of the CNS midline cells.
School Location:USA - Massachusetts
Source Type:Master's Thesis
Date of Publication:01/01/1997