Drosophila semaphorin2b is required for the axon guidance of a subset of embryonic neurons

Abstract

Background: The process of axon guidance is important in establishing functional neural circuits. The differential expression of cell-autonomous axon guidance factors is crucial for allowing axons of different neurons to take unique trajectories in response to spatially and temporally restricted cell non-autonomous axon guidance factors. A key motivation in the field is to provide adequate explanations for axon behavior with respect to the differential expression of these factors. Results: We report the characterization of a predicted secreted semaphorin family member, semaphorin2b (Sema-2b) in Drosophila embryonic axon guidance. Misexpression of Sema-2b in neurons causes highly penetrant axon guidance phenotypes in specific longitudinal and motoneuron pathways; however, expression of Sema-2b in muscles traversed by these motoneurons has no effect on axon guidance. In Sema-2b loss-of-function embryos, specific motoneuron and interneuron axon pathways display guidance defects. Specific visualization of the neurons that normally express Sema-2b reveals that this neuronal cohort is strongly affected by Sema-2b loss-of-function alleles. Conclusions: While secreted semaphorins have been implicated as cell non-autonomous chemorepellants in a variety of contexts, here we report previously undescribed Sema-2b loss-of-function and misexpression phenotypes that are consistent with a cell-autonomous role for Sema-2b. Developmental Dynamics 242:861–873, 2013. © 2013 Wiley Periodicals, Inc.Key FindingsMisexpression of the secreted semaphorin Sema-2b in neurons results in specific axon guidance phenotypes.Both Sema-2b loss-of-function and misexpression phenotypes are congruent with a cell-autonomous role for Sema-2b.Novel axon guidance phenotypes caused by Sema-2b loss-of-function mutations are characterized.

Differential ligand regulation of PlexB signaling in motor neuron axon guidance in Drosophila

“…In addition, embryos homozygous for either Sema‐2a B65 or Sema‐2b C4 sometimes exhibit ectopic innervations and lack of innervation at the 7/6 muscle cleft, consistent with previous observations (Fig. 1B, C; Winberg et al, 1998b; Emerson et al, 2013). While these ectopic innervations indicate targeting errors, lack of innervation appears to result from a failure in either selective defasciculation or attraction.…”

“…Sema‐2a is primarily expressed in the ventral nerve cord (VNC) and weakly in all body wall muscles, whereas Sema‐2b mRNA is detected in the VNC but not in muscles during embryonic development (Emerson et al, 2013; Kolodkin et al, 1993; Winberg et al, 1998b; Wu et al, 2011). Whether or how Sema‐2a and Sema‐2b regulate PlexB signaling in PNS motor axon guidance remains to be clarified.…”

“…1C). Based on attractive guidance function of Sema‐2b played in CNS longitudinal connectives and motor axons (Emerson et al, 2013; Wu et al, 2011), these defects suggest that Sema‐2b could also play an attractive function in ISNb motor axons as in CNS. Some ISNb axons of Sema‐2ab A15 , which contain a double null allele for both Sema‐2a and Sema‐2b (Wu et al, 2011), and PlexB KG00878 homozygous null mutants showed defasciculation defects similar to those observed in either Sema‐2a or Sema‐2b null mutants (Figs.…”

“…2C, E). Given the opposing effects and distinct expression patterns of Sema‐2a and Sema‐2b (Emerson et al, 2013; Kolodkin et al, 1993; Winberg et al, 1998b; Wu et al, 2011), these innervation defects also seem to be due to a failure in either repulsive or attractive guidance. In addition, we observed that embryos homozygous for the PlexB KG00878 null allele show two distinct SNa guidance defects: stall phenotypes in 21.2% of hemisegments and double turn phenotypes in 18.2% of hemisegments (Fig.…”

Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins

“…Sema-2a and Sema-2b show 70% amino acid identity and have been demonstrated to function redundantly in certain tissues (Sweeney et al, 2011; Wu et al, 2011). The secreted Semas are both expressed in the developing nerve cord at the time of commissure formation and both proteins are found to decorate the anterior and posterior commissures (Figure S5)(Emerson et al, 2013; Kolodkin et al, 1993; Wu et al, 2011). Sema-2a, however, displays a distinct enrichment at the midline (Figure S5) (Kolodkin et al, 1993; Wu et al, 2011).…”