P1: The role of the Dead end protein in controlling germ cell fate

Erez Raz, Institute of Cell Biology (Homepage)

Project summary

A live wild type zebrafish embryo with GFP-labelled germ cells at the region where the gonad develops (left) and an embryo in which the cells migrate and differentiate abnormally due to the lack of Dead end protein (right).

Zebrafish germ cells are an excellent vertebrate model for studying the development of the germline, and for understanding pathological conditions this cell lineage is associated with. A unique advantage of this model is the ability to study the function of proteins in regulating germ cell behaviour and differentiation employing live imaging in vivo and genetic manipulations.

The Dead end protein plays a central role in controlling the fate of germline cells in all vertebrates, and its loss of function results in sterility and the teratoma formation. Within the CRU we have recently shown that in the absence of Dead end, zebrafish germ cells fail to follow their differentiation program and instead are transformed into cells of other lineages. To determine the precise role of Dead end at different stages of germ-cell development we will establish methods that allow knocking down Dead end at different time points. The consequences of such manipulations on the expression of RNA molecules and on germ-cell specific structures will be determined by RNA sequencing experiments and microscopy. Together, these results and studies derived from them in mouse and human will shed light on the molecular machinery controlling the development of the germline and gametogenesis in vertebrates.

Project scheme.