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bioRxiv · 10.64898/2025.12.30.697122

GCL pruning of PIP3 establishes the soma-germline boundary

Saiduddin, M.·Pae, J.·Vidal, A. M.·Alani, M.·Lehmann, R.
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Abstract

Primordial germ cells (PGCs) are the first cells specified in the Drosophila embryo and serve as precursors to the germline. Their formation requires suppression of somatic fates, a process achieved by excluding the receptor tyrosine kinase Torso from the posterior pole through degradation mediated by the ubiquitin ligase adaptor Germ Cell-Less (GCL). Although Torso is known to antagonize PGC formation, the underlying mechanism has remained unclear. Here, we combine optogenetic Ras activation and Ras effector loop mutants to show that Ras signaling suppresses PGC formation independently of the canonical Raf/MEK/ERK pathway. We identify an unexpected early role for Torso in activating phosphoinositide 3-kinase (PI3K), generating posterior membrane domains enriched in phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Elevated PI3K activity disrupts PGC formation, while reduced PI3K activity leads to ectopic PGCs. We further demonstrate that GCL remodels the posterior pole membrane by suppressing Torso-dependent PI3K activation. Clearing PIP3 enables Myosin II enrichment, thereby constricting the pole bud for PGC formation. Together, our findings reveal how antagonistic Torso and GCL activities establish the soma-germline boundary by regulating cortical lipid organization. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/697122v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1efe138org.highwire.dtl.DTLVardef@1ab3b17org.highwire.dtl.DTLVardef@b49412org.highwire.dtl.DTLVardef@1655c5e_HPS_FORMAT_FIGEXP M_FIG Graphical AbstractO_LIMembrane domains with high Torso activity (purple) in the early embryo have a higher PIP3 content. C_LIO_LIAt the posterior pole, GCL-containing germplasm (green) degrades Torso, resulting in a PIP3-low membrane. C_LIO_LIClearing PIP3 enables Myosin II pole bud constriction required for PGC formation. C_LI C_FIG

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Saiduddin, M., Pae, J., Vidal, A. M., Alani, M., Lehmann, R.. 2025-12-31. GCL pruning of PIP3 establishes the soma-germline boundary. https://doi.org/10.64898/2025.12.30.697122

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