Stem cell behaviour in their niches and epithelial morphogenesis

Higher eukaryotes contain populations of stem cells responsible for the homeostasis of adult organisms. These cells are required also for tissue and organ repair after injury or disease. Stem cells are found generally in microenvironments or “niches” that regulate their proliferation and prevent the pull towards differentiation characteristic of most cell types. One such a niche has been described in the Drosophila ovary, which contains two populations of stem cells, one of germline origin (Germline Stem Cells; GSCs) and one of somatic origin that are ultimately responsible for the continuous production of new eggs during adulthood. The correct functioning of the niche relies, among other factors, on stem cell-niche support cell signalling and on the extracellular matrix (ECM).The correct epithelialisation of developing tissues is essential for proper organ morphogenesis and maintenance. Egg chamber production in the Drosophila ovary requires the generation of new epithelia that surround growing germline cysts and that form precisely patterned monolayered sheaths. Thus, the fruit fly ovary represents an excellent system in which to study epithelial morphogenesis from stem cell precursors.

In our laboratory, we study the biology of the GSC niche from genetic, cellular and molecular perspectives and the cellular and genetic mechanisms underlying proper follicular epithelium formation. In more detail, we focus our efforts on the following aspects of stem cell and epithelial biology:

1- We have previously defined a role for the ECM in niche maintenance and homeostasis. At present, we try to understand how the specialised ECM found in the niche regulates stem cell activity.

2- Using a combination of genomics, cell sorting and genetic approaches, we are studying how ageing modulates niche function. Currently, we are focusing our efforts on the role of splicing during niche ageing.

3- Our results show that integrins (ECM-cell cytoskeleton adhesion molecules, able too of mediating cell-ECM signalling) are required to prevent follicular epithelium stratification. In collaboration with the group of Lola Martín-Bermudo (CABD), we intend to use live microscopy to analyze follicle cell division and the role of integrins during follicular epithelium development.