The overall objective of this proposal is to establish a genome-wide, cell type-specific, computer-based searchable map of gene expression associated with critical periods of development of the normal fetal testis. The fetal testis plays an essential role in normal male urogenital tract development and many male urogenital tract disorders are linked to fetal testis perturbations. To understand the impact of genetic and environmental influences on testicular development, it is essential to determine normal gene expression patterns in the fetal testis during development. The goals of this proposal are to 1) define the 3-dimensional (3-D) spatial gene dynamics in relationship to structural development and hormonal balance in the developing testis and 2) identify cell-specific genes that can be used as biomarkers for key differentiation events. This information will provide researchers with valuable tools for further investigations into normal fetal testicular development as well as the causes, treatment, and prevention of male urogenital tract disorders.
Approach
To achieve our goals, laser capture microdissection of select regions within the fetal testis during late gestation (gestation days 14-18) will be combined with microarray analysis to characterize global gene expression. In situ hybridization will be used to identify gene expression in specific cell types. These data will be combined with a computerized structural mesh of the fetal testis to create a 3-D spatial and temporal gene expression model.
Relationship to the Overall Goals of GUDMAP
This project will create a detailed, high resolution atlas of gene expression in the developing fetal testis. Additional information will also be obtained at a lower resolution of gene expression throughout the developing urogenital system. When combined with the other projects associated with this consortium that focus primarily on other organs within the developing urogenital tract, a detailed, high resolution, searchable database will be created of global gene expression within the urogenital system throughout fetal development.