# Spatiotemporal regulation of collective cell behaviors in Drosophila > **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2022 · $580,495 ## Abstract Normal tissue development and tumor metastasis require extensive cell movements, and border cell migration in the Drosophila ovary provides a powerful in vivo model. Border cells migrate as a group of two different cell types, a pair of non-migratory polar cells in the center that recruit 6-8 epithelial cells to surround and carry them between nurse cells to the developing oocyte, in a structure called an egg chamber. Using this system, we first discovered the in vivo role of the 21kD GTPase Rac in protrusion and migration, then showed that photoactivation of Rac in one cell could steer the entire cluster. For more than two decades though, we were puzzled that expression of constitutively active Rac in border cells seemed to destroy the entire egg chamber. During the current funding period, we solved this longstanding mystery. We discovered that border cells expressing active Rac kill the nurse cells. Anterior follicle cells normally engulf and kill nurse cells late in oogenesis, and we propose that active Rac prematurely activates this program. A similar mechanism may explain otherwise mysterious immune deficiencies in human patients. Here we propose to continue our exciting investigation of the spatiotemporal control of Rac-mediated cell migration and engulfment in Drosophila. In Aim 1 we propose to elucidate the mechanisms of Rac-mediated cell killing. Taking advantage of the border cell model, we will test the functional effects of each of the known activating Rac mutations that cause immunodeficiencies in patients. We will test the hypothesis that border cells expressing active Rac prematurely activate the normal developmental killing program, and we will define more precisely the role of Rac within the molecular pathway. We will investigate how just six cells can destroy an entire egg chamber, and we will identify the chemical, physical, and adhesive properties that govern target cell selection. In Aim 2, we propose to follow up on our discovery that a basally localized Rac activator is required for border cell cluster cohesion and migration. We will elucidate its relationship to basolateral complex proteins and test whether its primary function is to localize Rac activity to basal surfaces. We will test the hypothesis that basal Rac activity is required to generate basal protrusions that in turn coordinate collective cell behavior. In Aim 3, we will follow up on a screen in which we have identified Rho family activators and inhibitors required in border cells. We propose that border cells require elaborate spatiotemporal control of Rac due to their needs to: maintain apicobasal polarity despite being detached from basement membrane, extend and retract forward-directed protrusions, maintain cohesion under strain, and inhibit inappropriate protrusion. Our ultimate goal is the decipher the Rac regulatory network. ## Key facts - **NIH application ID:** 10366848 - **Project number:** 2R01GM046425-30 - **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA - **Principal Investigator:** Denise J. Montell - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $580,495 - **Award type:** 2 - **Project period:** 1991-08-01 → 2026-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10366848 ## Citation > US National Institutes of Health, RePORTER application 10366848, Spatiotemporal regulation of collective cell behaviors in Drosophila (2R01GM046425-30). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10366848. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*