Overview and In-depth questions

Overview of germline stem cell unit formation

The adult ovary contains about 18 functional stem cell units, which form during larval development. These units contain at least three types of somatic cells and germ cells. To form these units, somatic precursors and germ cell precursors must first proliferate. They then differentiate to form niches and germline stem cells.

At the end of embryonic development,

the ovary is composed of very few Primoridal Germ Cells (Green) and a few somatic cells ( Red).

By the end of larval development,

all the components that make the stem cell unit have formed. The somatic niches are composed of Terminal Filament (between parallel lines) and Cap cells (arrowheads). Attached to cap cells are the newly established Germ Line stem Cells (GSCs, outlined). Posterior to GSCs are differentiating germ cells (Green).

The functional stem cell unit

The somatic niche (Red) includes Terminal Filament and Cap cells (arrowheads). GSCs are attached to Cap cells (outlined). As the GSC daughters leave the niche, they differentiate (Green), and divide to form germ line cysts (arrows).

We continue our search for novel genes controlling stem cell establishment and niche formation using

high-throughput approaches and genetics

Our Major Questions

How is the proliferation of somatic cells and germ cells coordinated such that there is no excess of deficiency of any cell type?

Many of the pathways that control ovarian cell proliferation (EGFR, STAT, InR) are known promoters of hyperplasia and tumor formation. As we continue to study these pathways, we find novel and conserved regulators, as well as novel ways in which these pathways interact. These data are importnat not only for understanding organogenesis but also for understanding tumor formation and metastasis.

What are the factors that control niche specification?

Very little is known about the early events in the formation of niches. Our studies led us to find some novel niche regulators and ways on which they control both niche formation and germline stem cell differentiation.

The notion that niche development is coupled to the development of the stem cells that will reside in it, is very exciting.

We keep 'hunting' for novel genes that speciy niches, and their possible effects on germ line stem cells.

What are the difference between Germ line stem cells and their precursors?

Germ line stem cells are asymmetric, localizing specific proteins and organelles close the the niche. However, their precursor cells, Primordial Germ Cells (PGCs) show no asymmetry.

We are interested in understanding the molecular basis for the initiation of asymmetry. We also wonder what other changes differentiate between precursor cells and stem cells. Such questions lie at the heart of understanding 'stemness'.

How is the differentiation of niches and germ cells coordinated, such that niches will differentiate prior to germ cells?

We have discovered that active mechanisms prevent Primordial Germ Cells (PGCs), the precursors of Germ Line Stem Cells (GSCs), from differentiation.

These mechanisms must prevent PGC diffenretiaiton until niches form. The niches (which maintain stem cells) can then protect stem cells from improper differentiation. One importnat coordinator of the developmental status of niches and stem cells is the transcription factor Broad. We study how Broad expression is controlled and which genes Broad regulate.