Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in zebrafish.

Background: Semaphorin (Sema)/Plexin (Plxn) signaling is important for many aspects of neuronal development, however, the transcriptional regulation imposed by this signaling pathway is unknown. Previously, we identified an essential role for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal precursor cells (RPCs) during early eye development. This study used RNA isolated from control, Sema6A-deficient and PlxnA2-deficient zebrafish embryos in a microarray analysis to identify genes that were differentially expressed when this signaling pathway was disrupted. Results: We uncovered a set of 58 transcripts, and all but 1 were up-regulated in both sema6A and plxnA2 morphants. We validated gene expression changes in subset of candidates that are suggested to be involved in proliferation, migration or neuronal positioning. We further functionally evaluated one gene, rasl11b, as contributing to disrupted proliferation in sema6A and plxna2 morphants. Our results suggest rasl11b negatively regulates proliferation of RPCs in the developing zebrafish eye. Conclusions: Microarray analysis has generated a resource of target genes downstream of Sema6A/PlxnA2 signaling, which can be further investigated to elucidate the downstream effects of this well-studied neuronal and vascular guidance signaling pathway. Developmental Dynamics 246:539-549, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]