Genetic basis for developmental homeostasis of germline stem cell niche number: a network of Tramtrack-group nuclear BTB factors.

Genetic basis for developmental homeostasis of germline stem cell niche number: a network of Tramtrack-group nuclear BTB factors. Mathieu Bartoletti^1,2,3*, Thomas Rubin^2,3, Fabienne Chalvet^2,3,4, Sophie Netter^1,2,3, Nicolas Dos Santos^2,3, Emilie Poisot^2,3, Melanie Paces-Fessy^2,3,5, Delphine Cumenal⁵, Frederique Peronnet⁵, Anne-Marie Pret^1,2, Laurent Theodore^1,2,4. 1) Centre de Génétique Moléculaire - UPR 3404, GIF SUR YVETTE, France; 2) Departement de Biologie, Univ Versailles St-Quentin, Versailles, France; 3) Laboratoire de Génétique et Biologie Cellulaire, Equipe Associée 4589, Univ Versailles St-Quentin, Versailles , France; 4) Departement de Biologie, Univ Paris-Sud, Orsay, France; 5) Biologie du Développement UMR 7622, CNRS et UPMC, France.

In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles varies widely among species. It remains generally unknown how the number of stem cell niches is controlled in the ovary. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8-10 cells that pile up and sort in stacks. TFs constitute organizers of individual GSC niches during larval and early pupal development. In the melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of GSC niches.