dc.description.abstracteng | Adult stem cells are found in most adult tissues where they are responsible for
replacing cells that are lost due to turnover or injury. They have the unique ability
to give rise to differentiated progeny, while at the same time maintaining the stem
cell population. In order to preserve tissue homeostasis, these two processes:
maintenance versus differentiation have to be tightly regulated. It was shown
that surrounding cells form a specific microenvironment, the stem cell niche, that
controls the stem cell behavior. The results described in the present thesis show
that stem cell progeny differentiation also requires specific interactions with the
surrounding cells, the differentiation niche.
The D. melanogaster germarium provides an excellent model to study these
interactions since adult stem cell maintenance and adult stem cell progeny differentiation
can be analyzed in the same well characterized and easy to genetically
manipulate organ.
We found that components of the ecdysteroid signaling pathway play a role
in the germarium. It had been shown previously that ecdysteroids are required
for later stages of oogenesis; the present thesis describes how ecdysteroids control
the progression through the early stages of germline differentiation. Ecdysone
signaling perturbations lead to a germline stem cell progeny differentiation delay.
These delayed germline cells display a stem cell-like chromatin state; however,
based on the analysis of specific markers, they are not stem cells. Differentiation
markers also are not present, indicating that these germline cells are delayed at
the pre-cystoblast to cystoblast transition.
Interestingly, we found that the ecdysone signaling pathway is acting on the
germline cells in a cell non-autonomous way via the somatic germarial cells, a
process that requires the spatially restricted cofactors Taiman and Aprupt, activator
and inhibitor of ecdysone signaling. Deficit of ecdysone signaling during
the development leads to enlarged functional niches, somatic cell differentiation
defects and a confused sexual identity. The somatic escort cells fail to appropriately
differentiate in the absence of functional ecdysone signaling: shape, division
and cell adhesive characteristics are altered; cytoplasmic protrusions, required for
interacting with the germline, are not formed and escort cells form a columnar-like
epithelium. The cell adhesion proteins Armadillo and DE-Cadherin are found at
higher levels in mutant escort cells; which subsequently affects the germline cells
responsiveness to Wg signaling. Dampening of Wg signaling in the germline leads
to a germline differentiation delay.
Furthermore, the miRNA let-7 is modulating the tissue and time specific response
to ecdysone via regulating the levels of Abrupt, that is both an inhibitor of ecdysone signaling and a potent regulator of epithelial cell fate. miRNA let-7
is induced by steroids, targets Ab and acts in a feedback loop to ensure the robustness
of ecdysone signaling in escort cells in response to changing internal and
external conditions such as aging, stress and nutrition. | de |