Astrocyte growth during morphogenesis is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor

Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1, likely acting through Rac1, is required for astrocytes to elaborate their complex morphology in vivo. The lipid phosphate phosphatases Wunen/Wunen2, which process phospholipid ligands, also regulate astrocyte morphology, and, via Tre1, mediate astrocyte-astrocyte competition for growth promoting lipids. Loss of s1pr1, the functional analog of Tre1 in zebrafish disrupts astrocyte process elaboration. Live-imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during morphogenesis, and that S1pr1 signaling is required throughout astrocyte development. Tre1 and S1pr1 are thus potent evolutionarily conserved regulators of astrocyte growth and elaboration of morphological complexity. O_LIThe GPCR Tre1 and LPPs Wun/Wun2 promote astrocyte process outgrowth in Drosophila C_LIO_LIAstrocytes compete for a growth{-}promoting phospholipid in the CNS C_LIO_LIWun/Wun2 act locally to regulate process outgrowth through Tre1 C_LIO_LIVertebrate S1pr1 regulates astrocyte growth early, through modulation of process dynamics C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/508188v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1e86db5org.highwire.dtl.DTLVardef@7abd6borg.highwire.dtl.DTLVardef@29f163org.highwire.dtl.DTLVardef@1a6c4b9_HPS_FORMAT_FIGEXP M_FIG C_FIG