Decoupling axonal regrowth and branching through Imp-dependent RNA regulation during neuronal remodeling

Abstract

Structural remodeling of neuronal projections in response to developmental cues, injury, or disease is essential for adaptive circuit rewiring. This dynamic process, characterized by pruning and regrowth phases, requires the coordinated execution of neurite regrowth and branching to establish functional neuronal circuits. Yet, how these processes are regulated in space and time at the post-transcriptional level remains poorly understood. Here, we identify the conserved RNA-binding protein Imp (IGF2BP) as a central regulator of developmental axonal remodeling in Drosophila CCAP/Bursicon neurons. We show that Imp acts within a restricted time window during late metamorphosis to control both late regrowth and branching of adult CCAP/Bursicon axons. Combining functional approaches, high-resolution imaging and single-molecule mRNA detection, we further show that Imp controls these temporally distinct programs through genetically separable regulatory mechanisms. While axonal elongation is mediated by Imp-dependent stabilization of profilin mRNA, axonal branching is mediated by an independent mechanism that may involve local regulation in axons. Together, our findings demonstrate that axonal regrowth and branching, two morphogenetic events essential for neuronal circuit maturation in vivo, are controlled independently, yet coordinated through a common and conserved post-transcriptional framework. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/740905v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1ca291corg.highwire.dtl.DTLVardef@15108daorg.highwire.dtl.DTLVardef@11c5741org.highwire.dtl.DTLVardef@1a4773a_HPS_FORMAT_FIGEXP M_FIG C_FIG