ABSTRACT
Semaphorin6A (Sema6A) is a repulsive guidance molecule that plays many roles in central nervous system, heart and bone development, as well as immune system responses and cell signaling in cancer. Loss of Sema6A or its receptor PlexinA2 in zebrafish leads to smaller eyes and improper retinal patterning. Here, we investigate a potential role for the Sema6A intracellular domain in zebrafish eye development and dissect which phenotypes rely on forward signaling and which rely on reverse signaling. We performed rescue experiments on zebrafish Sema6A morphants with either full-length Sema6A (Sema6A-FL) or Sema6A lacking its intracellular domain (Sema6A-ΔC). We identified that the intracellular domain is not required for eye size and retinal patterning, however it is required for retinal integrity, the number and end feet strength of Müller glia and protecting against retinal cell death. This novel function for the intracellular domain suggests a role for Sema6A reverse signaling in zebrafish eye development.
Footnotes
Author contributions
Conceptualization: C.M.D., R.M.S., A.M.L., B.A.B., A.M.E.; Methodology: C.M.D., A.M.E.; Validation: C.M.D.; Formal analysis: C.M.D., A.M.E.; Investigation: C.M.D., B.A.B., A.M.E.; Resources: B.A.B., A.M.E.; Data curation: C.M.D., A.M.L.; Writing - original draft: C.M.D., A.M.E.; Writing - review & editing: C.M.D., R.M.S., A.M.L., B.A.B., A.M.E.; Visualization: C.M.D.; Supervision: B.A.B., A.M.E.; Project administration: C.M.D., B.A.B., A.M.E.; Funding acquisition: B.A.B., A.M.E.
Funding
This work was supported by the National Science Foundation (NSF) IOS grants 1021795 and 1625154 to B.A.B. and A.M.E., and NSF DBI REU grant 126786 to B.A.B. and A.M.E.
Data availability
All relevant data can be found within the article and its supplementary information.
