Jennifer Jemc Mierisch
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, and infertility in the case of gonad defects. 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 (Figure 1). 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.
Figure 1. Gonad formation in the Drosophila embryo. (A) Germ cells (GCs) exit the midgut and migrate to somatic gonadal precursor cells (SGPs) in parasegments 10-12 at stage 12. At this stage SGPs are migrating and beginning to intermingle with GCs. The set of three distinct SGPs cluster found bilaterally in the embryo are beginning the process of cluster fusion to form a cohesive organ. (B) GCs intermingle with and are ensheathed by SGPs, and SGP cluster fusion is complete by stage 13. The gonad begins to compaction to its final, spherical structure. (C) GCs and SGPs have undergone compaction and coalescence into a rounded gonad by stage 15.
Jemc, J. C., Milutinovich, A. B., Weyers, J. J., Takeda, Y., and M. Van Doren. (2012) raw Functions through JNK signaling and cadherin-based adhesion to regulate Drosophila gonad morphogenesis. Dev. Biol. 367, 114-125.
Jemc, J. C. (2011) Somatic Gonadal Cells: The Supporting Cast for the Germline. Genesis. 49, 753-75. Invited Review
Weyers, J. J., Milutinovich, A. B., Takeda, Y., Jemc, J. C., and M. Van Doren. (2011) A genetic screen for mutations affecting gonad formation in Drosophila reveals a role for the slit/robo pathway. Dev. Biol. 353, 217-228.
Jemc, J. and I. Rebay. (2007) Identification of Transcriptional Targets of the Retinal Determination Gene eyes absent. Dev. Biol. 310, 416-29.
Jemc, J. and I. Rebay. (2007) The Eyes Absent Family of Phosphotyrosine Phosphatases: Properties and Roles in Developmental Regulation of Transcription. Annu. Rev. Biochem. 76, 513-38. Review
Jemc, J. and I. Rebay. (2006) Targeting Drosophila eye development. Genome Biol. 7, 226. Review
Jemc, J. and I. Rebay. (2006) Characterization of the split ends-like gene spenito reveals functional antagonism between SPOC family members during Drosophila eye development. Genetics 173, 279-86.
Sloper-Mould, K. E., Jemc, J., Pickart, C. M., and L. Hicke. (2001) Distinct functional surface regions on ubiquitin. J. Biol. Chem. 276, 30483-9.