Developmental axon regrowth and primary neuron sprouting utilize distinct actin elongation factors

Abstract

Intrinsic neurite growth potential is a key determinant of neuronal regeneration efficiency following injury. The stereotypical remodeling of Drosophila γ-neurons includes developmental regrowth of pruned axons to form adult specific connections, thereby offering a unique system to uncover growth potential regulators. Motivated by the dynamic expression in remodeling γ-neurons, we focus here on the role of actin elongation factors as potential regulators of developmental axon regrowth. We found that regrowth in vivo requires the actin elongation factors Ena and profilin, but not the formins that are expressed in γ-neurons. In contrast, primary γ-neuron sprouting in vitro requires profilin and the formin DAAM, but not Ena. Furthermore, we demonstrate that DAAM can compensate for the loss of Ena in vivo. Similarly, DAAM mutants express invariably high levels of Ena in vitro. Thus, we show that different linear actin elongation factors function in distinct contexts even within the same cell type and that they can partially compensate for each other.

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

“…As suggested by Yamamoto, Bellen and colleagues (Yamamoto et al, 2014), Pldo/ZSWIM8 appears to be linked to a genetic disorder in humans affecting the nervous system. This observation could be explained by our data regarding its function in the regulation of actin cytoskeletal dynamics, as biogenesis of neurites requires a highly regulated actin polymerization network (Ben-Yaacov et al, 2001; Korobova and Svitkina, 2008; Matusek et al, 2008; Santos et al, 2002; Tahirovic et al, 2010; Yaniv et al, 2020). For example, linear actin polymerization is required for radial glial migration and in the initial stages of neurite formation and branched polymerization is essential for their maturation.…”

“…Dsh accumulates at the apico-distal zone of Drosophila wing cells, where it is thought to recruit and activate RhoA, Rac, and Daam1 (Disheveled-associated activator of morphogenesis 1, originally identified in Xenopus (Habas et al, 2001). Daam1 and likely also other formins, like Dia (as Daam1 appears to be redundant in this wing hair context), interact with Profilin to induce actin polymerization (Adler, 2012;Barko et al, 2010;Goodrich and Strutt, 2011;Matusek et al, 2008;Singh and Mlodzik, 2012;Yaniv et al, 2020). The pldo/zswim8 LOF phenotype is rescued by Dia or Profilin overexpression, while different isoforms of dDaam1, including activated ones (Matusek et al, 2006), do not rescue pldo/zswim8 LOF defects, consistent with the notion that Dia and not Daam1 is the critical formin family member in this context.…”

The conserved Pelado/ZSWIM8 protein regulates actin dynamics by promoting linear actin filament polymerization

“…As suggested by Yamamoto, Bellen, and colleagues ( Yamamoto et al, 2014 ), Pldo/ZSWIM8 appears to be linked to a genetic disorder in humans affecting the nervous system. This observation could be explained by our data regarding its function in the regulation of actin cytoskeletal dynamics as biogenesis of neurites requires a highly regulated actin polymerization network ( Ben-Yaacov et al, 2001 ; Korobova & Svitkina, 2008 ; Matusek et al, 2008 ; Tahirovic et al, 2010 ; Yaniv et al, 2020 ; and rev. in Da Silva and Dotti [2002] ).…”

“…Dsh accumulates at the apico-distal zone of Drosophila wing cells, where it is thought to recruit and activate RhoA, Rac, and Daam1 (disheveled-associated activator of morphogenesis 1, originally identified in Xenopus) (Habas et al, 2001). Daam1 and likely also other formins, like Dia (as Daam1 appears to be redundant in this wing hair context), interact with Profilin to induce actin polymerization (Matusek et al, 2008;Barko et al, 2010;Yaniv et al, 2020;and rev. in Goodrich and Strutt [2011], Adler [2012], and Singh and Mlodzik [2012]).…”

Transneuronal Dpr12/DIP‐δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons

“…Based on these results, we conclude that Dpr12 is cell-autonomously required in c-KCs for their full developmental regrowth. Interestingly, unlike other mutants that affect developmental regrowth (Yaniv et al, 2012;Yaniv et al, 2020), dpr12 mutant axons seem to partially regrow but stop prematurely in a particular and stereotypic location along the lobe. Therefore, and given that the clobe is divided into distinct zones, we next mapped the location of and EV3).…”