The  Elkouby Lab

Our Research

Germ cells are at the basis of reproduction and undergo fascinating processes during their development. Unlike many other tissues where cells perform a collective tissue function, germ cells differentiate in the gonad to perform an individual function. The oocyte gives rise to the egg, a single cell that contains the building blocks that initiate the early events of embryonic development following fertilization.

The oocyte undergoes a dramatic differentiation process (see figure below) that begins when germline stem cells divide and produce the oogonia, a mitotic precursor cell of the differentiating meiotic oocyte. Oogonia divide incompletely to generate early oocytes that are inter-connected to sister oocytes via cytoplasmic bridges in a cellular organization called the germline cyst. Meiosis initiation transforms the oogonia in the cyst into differentiating oocytes that then separate and become surrounded by somatic granulosa cells in the follicle. In the early differentiating oocyte dramatic nuclear events underlie meiosis, while the cytoplasm in most species becomes polarized. Notably, these intracellular processes occur simultaneously with the changes in cellular organization, all while the oocyte significantly grows in volume.

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How are these events mechanistically executed and controlled? How are they collectively coordinated by the cell in time and space? How are they developmentally coordinated across cells? To address these questions, we established the zebrafish juvenile ovary as an excellent model for early oogenesis. We have discovered a novel cellular organizer, we termed the Centrosome Organizing Center (COC) (figure below), that integrates these multiple key facets of the early differentiating oocyte. We are now investigating the mechanisms and regulation of the COC various functions.

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Our analyses in the early ovary now enable the investigation of further key processes of oogenesis, such as how germline stem cells give rise to oogonia and oocytes, what are the functional contributions of the germline cyst, how oocytes then transition from a cyst organization to form a follicle, and more. Altogether, aim to construct a comprehensive mechanistic view of early oogenesis.

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These events, from the germline stem cells and oogonia, through differentiation in the cyst, and formation of the follicle, represent critical stages of oogenesis, and are conserved between zebrafish and mammals. In mammals, they occur during pre-natal and early post-natal development and impact female reproduction throughout life. In mice, only ~20% of the initial germ cell pool eventually form a follicle. These processes thus determine the number of follicles a female would have for life, but still present many open questions. The new model of the zebrafish ovary provides an excellent system to better understand these processes and advance our knowledge of female reproduction and health.