Role of dynamic JNK signalling in balancing cell removal and renewal in a stressed epithelium

Tissue homeostasis requires a tight maintenance of cell number.

Little is known about how tissue size and cell numbers are maintained in stress situations, when additional proliferation is needed to compensate for cell loss.

I propose to study the homeostatic response to stress in a tissue (Drosophila wing primordia) in which Ribosomal Proteins-deficiency causes extensive apoptosis compensated by extra proliferation. How are these two responses balanced to ensure the emergence of a normal adult organism? JNK signalling is a strong candidate to mediate both apoptosis and proliferation responses.

I propose to decipher the regulatory events that control this two-faced response, and to identify the proliferative pathways activated by JNK.

Using the latest tools of genome engineering and live imaging, I aim at unravelling the spatio-temporal dynamics of JNK signalling and the downstream activation of cell death or division.

Next, I will use a candidate gene and an unbiased approaches to uncover the transcriptional programs that correlate with apoptosis and proliferation.

Lastly, I will verify the relevance of the identified candidates and investigate their spatial-temporal activity upon JNK activation.

The results will be key to reaching the next stage of understanding the role of JNK in orchestrating the concerted replacement of lost cells that ultimately results in functional epithelia.

Uncovering this logic in a relatively simple epithelium will hopefully guide further studies in more complex tissues of direct biomedical relevance.