Research
TopicsDepartment of Cell and Structural Biology
Ph.D. (1994) University of Colorado
Research
Topics
- Planarian regeneration
- Stem cell biology
- Germ line development
Research
Interests
The regenerative powers of many metazoans have intrigued biologists for generations and yet, the mechanisms involved in regenerative processes remain largely unknown. My laboratory uses the planarian flatworm, a classic subject of early regeneration experiments, to understand the molecular mechanisms underlying regeneration. A population of stem cells, referred to as neoblasts, endows the flatworm with its prodigious regenerative abilities.Research in my laboratory focuses on three main areas:
Control of the proliferation and differentiation of the regenerative stem cells: With Alejandro Sánchez Alvarado, we have generated a collection of expressed sequence tags (ESTs) from planarian heads, regeneration blastemas, and enriched neoblasts. Using these ESTs, we will generate microarrays to study global changes in gene expression throughout the regenerative process. By combining these studies with automated in situ hybridization and functional analysis using RNAi, we hope to understand the mechanisms by which stem cell proliferation is stimulated by wounding and how the differentiation of these stem cells is choreographed to replace the missing structures.
The factors that regulate germ cell differentiation: Unlike most other metazoans, planarians do not segregate their germ cell lineage during embryogenesis. Instead, the gonads are formed in specific regions of the adult animal, when it attains the appropriate size. Thus, there must be cues that direct the neoblasts to form ovaries and testes at the appropriate time and in the appropriate place. The cues that guide this determination of the germ cells in planarians are completely unknown.
The species that we have been studying, Schmidtea mediterranea, provides a unique opportunity to study this issue. S. mediterranea exists in both sexually and asexually reproducing strains; the sexual organisms are hermaphroditic and produce egg capsules when mated with another planarian, whereas the asexual organisms reproduce strictly by fission. From a molecular genetic standpoint, the asexuals are interesting because they harbor a Robertsonian translocation that results in a switch from sexual to asexual reproduction. Microarray analysis will be used to identify genes expressed in the sexual strain but lacking in the asexuals. In combination with automated, large-scale in situ hybridization studies, we will identify markers for the germ cells, as well as genes involved in germ cell determination in this rather simple metazoan. Such studies should provide insights into the evolution of germ cell determination mechanisms.
Neural regeneration and plasticity: One of the truly fascinating aspects of planarian biology is the plasticity of the nervous system. In addition to the rapid regeneration of cephalic ganglia, ventral nerve cords, and all of the sensory structures, the nervous system is plastic enough to grow and shrink with the planarian, depending upon the availability of food. Due to a lack of appropriate markers, little is know about the process of nervous system regeneration in planarians, or to what extent cell turnover in the nervous system allows the plasticity seen during growth and degrowth. To identify nervous system markers, ESTs from head-specific cDNA libraries are being screened by sequence similarity and automated in situ hybridization. With such markers in hand, we can begin a detailed analysis of nervous system regeneration in the planarian.
Key Words Regeneration, Cell proliferation and differentiation, Pattern
formation, Germ cell determination
Current Funding UIUC Startup Funds