Research Interests
Cell-cell interactions are critical for the establishment of tissue architecture during development and maintaining tissue function in the adult. The failure of a cell to make and maintain appropriate contacts with other cells can result in birth defects, the development and metastasis of tumors, infertility in the case of the gonad, and neuropathy and neurodegeneration in the nervous system.
Studies in the Gonad
The gonad provides an excellent model for studying how different cell types migrate, recognize each other, and establish cell-cell interactions for the development and maintenance of a functional organ. During development germ cells, which will give rise to sperm and egg, and somatic gonadal cells, which support germ cell development, are specified at different locations in the embryo. Both cell types must migrate and coalesce to form a functional organ (Figure 1). Defects in this process can lead to infertility or the formation of germ cell tumors. Using Drosophila as a model system, we are working to identify the molecular mechanisms that regulate the migration of the somatic cells of the gonad, and their ability to establish the cell-cell interactions required for a functional gonad.
Previously, we found that mutations in the gene raw cause a striking phenotype in which somatic gonadal precursor cells (SGPs) fail to intermingle with and ensheath the germ cells. These defects result in decreased germ cel l proliferation, and a failure of germ cells to initiate sex-specific gene expression. Investigation of the molecular context of raw function in the gonad revealed that RAW functions within the JNK signaling pathway to regulate subcellular localization of the transcription factor, Drosophila JUN. In addition, RAW also regulates germline-soma interactions via Drosophila E-cadherin. Currently, we are investigating the role of other genes that appear to affect germline-soma interactions. In particular, we are interested in how cell morphology is affected in these ensheathment mutants. Therefore, we are investigating how these mutations affect the morphology of somatic cells in order to gain greater insight into the role these genes play in gonad morphogenesis.
In addition to the importance of germline-soma interactions for proper gonad formation, SGPs must also migrate and interact with each other in processes known as SGP cluster fusion and compaction in order to form a functional gonad. We have identified a number of mutants that are defective in these processes. Currently, we are mapping these mutations to identify the genes that are affected. In addition, we have already identified a handful of genes required for cluster fusion and compaction. For these genes we are exploring the molecular context in which they function, using a combination of genetics, biochemistry, molecular biology, immunohistochemistry, live imaging, and bioinformatics. By using these approaches, we will gain further insight into the mechanisms regulating gonad morphogenesis, as well as identifying gene networks that are likely to function in other developmental and disease contexts.
Studies in the Nervous System
We are also interested in the molecular mechanisms underlying the establishment of neuron-glia interactions in the developing nervous system. Glia play a critical role in nervous system structure and function, ensheathing neurons to promote efficient function, providing trophic support, clearing debris, and forming the blood-brain barrier. The identification of genes that regulate cell-cell interactions in the gonad has led us to explore how these genes function in other developmental contexts, namely the developing nervous system. In particular, we are interested in genes that function in ensheathment of germ cells in the gonad, given the similarity of this event to ensheathment of neurons by glia. Using a combination of immunohistochemistry, genetics, and behavioral assays, we aim to further characterize the molecular mechanisms regulating glial development and the establishment of neuron-glia interactions.
Cell-cell interactions are critical for the establishment of tissue architecture during development and maintaining tissue function in the adult. The failure of a cell to make and maintain appropriate contacts with other cells can result in birth defects, the development and metastasis of tumors, infertility in the case of the gonad, and neuropathy and neurodegeneration in the nervous system.
Studies in the Gonad
The gonad provides an excellent model for studying how different cell types migrate, recognize each other, and establish cell-cell interactions for the development and maintenance of a functional organ. During development germ cells, which will give rise to sperm and egg, and somatic gonadal cells, which support germ cell development, are specified at different locations in the embryo. Both cell types must migrate and coalesce to form a functional organ (Figure 1). Defects in this process can lead to infertility or the formation of germ cell tumors. Using Drosophila as a model system, we are working to identify the molecular mechanisms that regulate the migration of the somatic cells of the gonad, and their ability to establish the cell-cell interactions required for a functional gonad.
Previously, we found that mutations in the gene raw cause a striking phenotype in which somatic gonadal precursor cells (SGPs) fail to intermingle with and ensheath the germ cells. These defects result in decreased germ cel l proliferation, and a failure of germ cells to initiate sex-specific gene expression. Investigation of the molecular context of raw function in the gonad revealed that RAW functions within the JNK signaling pathway to regulate subcellular localization of the transcription factor, Drosophila JUN. In addition, RAW also regulates germline-soma interactions via Drosophila E-cadherin. Currently, we are investigating the role of other genes that appear to affect germline-soma interactions. In particular, we are interested in how cell morphology is affected in these ensheathment mutants. Therefore, we are investigating how these mutations affect the morphology of somatic cells in order to gain greater insight into the role these genes play in gonad morphogenesis.
In addition to the importance of germline-soma interactions for proper gonad formation, SGPs must also migrate and interact with each other in processes known as SGP cluster fusion and compaction in order to form a functional gonad. We have identified a number of mutants that are defective in these processes. Currently, we are mapping these mutations to identify the genes that are affected. In addition, we have already identified a handful of genes required for cluster fusion and compaction. For these genes we are exploring the molecular context in which they function, using a combination of genetics, biochemistry, molecular biology, immunohistochemistry, live imaging, and bioinformatics. By using these approaches, we will gain further insight into the mechanisms regulating gonad morphogenesis, as well as identifying gene networks that are likely to function in other developmental and disease contexts.
Studies in the Nervous System
We are also interested in the molecular mechanisms underlying the establishment of neuron-glia interactions in the developing nervous system. Glia play a critical role in nervous system structure and function, ensheathing neurons to promote efficient function, providing trophic support, clearing debris, and forming the blood-brain barrier. The identification of genes that regulate cell-cell interactions in the gonad has led us to explore how these genes function in other developmental contexts, namely the developing nervous system. In particular, we are interested in genes that function in ensheathment of germ cells in the gonad, given the similarity of this event to ensheathment of neurons by glia. Using a combination of immunohistochemistry, genetics, and behavioral assays, we aim to further characterize the molecular mechanisms regulating glial development and the establishment of neuron-glia interactions.