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Feedback Loop Governing Ovarian Development Unraveled

rates how the ovary controls its amount of stem cell precursors, called primordial germ cells (PGCs). Primordial germ cells are important cells. Some of them develop into germline stem cells, which have regenerative powers and others will differentiate into eggs.

Signals, sensors, feedback

A fruit fly takes ten days to go from embryo to larva to pupa to flying insect. The researchers looked at a larval development phase during which the ovary grows remarkably fast. In three days the number of primordial germ cells rises from twelve cells to 100 cells.

The scientists started by looking at larvae with defects that cause them to have too few germ cells. The animal could well mature with this defect and suffer from reduced fertility. But it does not. Instead, they found that the ovary has a way to sense its lack of germ cells and steps up production. "Within three days, the ovary catches up; it then has enough germ cells," says Dr. Gilboa. "I had not a shred of a clue how this is accomplished, so I set out to understand how the ovary does this."

There were no experimental tools to let her study the entire process. She needed to be able to test many genes, many conditions, and find markers of those conditions so the results would be visible under the microscope every step of the way. Over several years, Dr. Gilboa developed both the methods and know-how to explore what she calls "a black hole": the process that transforms an embryonic ovary into an adult one.

As the painstaking experiments reveal, the two cell types that interact in a feedback loop through a signaling pathway are 1) primordial germ cells and 2) intermingled cells, which are neighboring somatic cells in the ovary.

The surface of the intermingled cells is pocked with epidermal growth factor (EGF) receptors, docking ports for signaling molecules. Dr. Gilboa found that primordial germ cells produce a protein called Spitz. This prote
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