Zebrafish germline development

Our lab is interested in understanding the mechanisms that regulate adult stem cell behavior in the context of an intact organisms. Stem cells are characterized by their ability to self-renew as well as give rise to differentiated progeny. Stem cells must be precisely regulated to avoid either stem cell loss or hyper-proliferation. There is mounting evidence that stem cells play a central role in the biology of cancers, including acute myelogenous leukemia (AML), breast, and brain cancers .

We use the zebrafish germline as a system to study adult stem cell behaior. Germline stem cells (GSC) are a particularly tractable stem cell population to study because 1) they localize to a discrete organ, the gonad, 2) they give rise to only one differentiated cell type- sperm in males and oocytes in females, and 3) GSC are not required for viability of the organism and therefore mutations that affect GSC behavior can be identified and studied in an organismal context. Understand the regulation of germline stem cells in vertebrates is relevant to cancer as most childhood malignancies are thought to result from germ cell-derived tumors and testicular cancer is the most common malignancy in men aged 20-35 years.

One of the attributes that make the zebrafish a popular organism for biological research is that adult females can produce mature eggs year-round, laying clutches of several hundred eggs on a near weekly basis. The ovaries of adult zebrafish are known to contain germ cells in all stages of oogenesis, from pre-follicle stage to mature eggs, suggesting that new follicles are continually recruited from a pool of pre-meiotic cells. The pre-follicle stage pool of germ cells (Stage Ia; Selman et al., 1993) all consist of cells that are 7-10 µm in diameter, and can be further divided into cells that appear to be in mitotic interphase (presumed GSC) and newly determined oocytes that are in prophase of meiosis I (leptotene-diplotene). Despite this compelling evidence, there is no functional evidence that proves the existence of germline stem cells in the zebrafish ovaries.