Identification of -Regulatory Region Controlling Semaphorin-1a Expression in the Embryonic Nervous System.

The transmembrane semaphorin Sema-1a mediates forward and reverse signaling that plays an essential role in motor and central nervous system (CNS) axon pathfinding during embryonic neural development. Previous immunohistochemical analysis revealed that Sema-1a is expressed on most commissural and longitudinal axons in the CNS and five motor nerve branches in the peripheral nervous system (PNS). However, Sema-1a-mediated axon guidance function contributes significantly to both intersegmental nerve b (ISNb) and segmental nerve a (SNa), and slightly to ISNd and SNc, but not to ISN motor axon pathfinding. Here, we uncover three -regulatory elements (CREs), , and , that robustly drove reporter expression in a large subset of neurons in the CNS. In the transgenic lines and reporter expression was consistently observed on both ISNb and SNa nerve branches, whereas in the line reporter expression was irregularly detected on ISNb or SNa nerve branches in small subsets of abdominal hemisegments. Through complementation test with a Sema1a loss-of-function allele, we found that neuronal expression of Sema-1a driven by each of and restores robustly the CNS and PNS motor axon guidance defects observed in Sema-1a homozygous mutants. However, when wild-type Sema-1a is expressed by in mutants, the PNS axon guidance phenotypes are partially rescued while the CNS axon guidance defects are completely rescued. These results suggest that in a redundant manner, the CREs, , and govern the Sema-1a expression required for the axon guidance function of during embryonic neural development.