Department of Biology
The University of Mississippi
Office: 122 Shoemaker Hall
Telephone: (662) 915-1700
- Molecular genetic mechanisms of nervous system development in Drosophila
We are interested in the development of the nervous system. A functional nervous system requires the correct specification and precise organization of a large number of neural cell types. These cell types include the neurons that transmit information and their glial support cells. Drosophila has proven to be an excellent model system for the study of mechanisms underlying neural development. In addition to its sophisticated classical and molecular genetic tools, much is known about the lineages, patterns, and identities of glia and neurons, and about the projections and pathways taken by axons in the developing CNS and PNS. Neurons and glia are arranged in a stereotypical pattern repeated in each segment. They are easily identified by position, and by a large array of markers. We take advantage of these features, using genetic and molecular approaches to uncover processes controlling neural cell fate specification and differentiation in Drosophila.
Ventral views of Drosophila embryos several hours before hatching. Anterior is at the top.
A) The nerve tracks of the central nervous system are labeled with an antibody that recognizes an epitope in the axons of interneurons (brown).
B) The nuclei of glial cells are labeled by an antibody against Repo protein (black), a transcription factor required for the proper differentiation of glia.
Glial versus neuronal cell specification We are studying how neural stem cells acquire glial versus neuronal fates. A major player in this process is the glial cells missing gene (gcm), a master regulator of glial cell fate in Drosophila. gcm encodes a novel DNA-binding transcription factor that is required for the development of nearly all glia in Drosophila. In the presence of Gcm protein, neural cells develop into glia, while in its absence they become neurons. Several mammalian gcm homologs have been identified, and they have been shown to have conserved biochemical and regulatory properties. We have demonstrated that glial cell determination is controlled by the precise regulation of gcm expression and activity in neural progenitors. Because gcm is transiently expressed, gcm can only initiate glial cell differentiation. Downstream genes must accomplish glial differentiation and maintenance of glial cell fate. To understand how glial cell development is controlled, we aim to understand how gcm transcription is activated in different neural lineages, what factors regulate Gcm activity, and what are the downstream genes that carry out glial cell differentiation.
gcm is a master regulator of glial cell fate in Drosophila. Glial cells in the embryonic CNS as revealed by anti-Repo staining in four adjacent abdominal segmental neuromeres.
A) Wild type embryo.
B) gcmloss-of function embryo results in the absence of glial cell development.
C) Panneural expression of gcm causes nearly all CNS cells to develop into glial cells expressing Repo.
gcm functions as a binary genetic switch for glia vs. neurons. The dorsal bipolar dendrite (BD) lineage in the peripheral nervous system.
A) BD neuron (arrowhead) and glial support cell (arrow) in a wild type Drosophila embryo.
B) gcm loss-of-function mutant embryo.
C) gcm gain-of-function embryo, in which a transgenic construct drives ectopic gcmexpression in presumptive neurons.
We are currently pursuing these aims through the following projects:
1) the molecular genetic characterization of cis-regulatory DNA elements controlling gcm transcription;
2) the identification and characterization proteins that modulate Gcm activity;
3) the molecular genetic characterization of cis-regulatory elements of the candidate gcm-target gene, repo; and,
4) a systematic classical Drosophila mutagenesis screen for genes that modify the expression and pattern of Repo protein, a glial specific marker that is directly regulated by gcm. We are also pursuing reverse genetic approaches to identify new genes that potentially regulate glial and neuronal development.