Agrin is Required for Posterior Development and Motor Axon Outgrowth and Branching in Embryonic Zebrafish

Although recent studies have extended our understanding of agrin's function during development, its function in the CNS is not clearly understood. To begin to address this question, zebrafish agrin was identified and characterized. Zebrafish agrin is expressed in the developing CNS and in non-neural structures such as somites and notochord. In agrin morphant embryos, acetylcholine receptor (AChR) cluster number and size on muscle fibers at the choice point were unaffected, while AChR clusters on muscle fibers in the dorsal and ventral regions of the myotome were reduced or absent. Defects in axon outgrowth by primary motor neurons, subpopulations of branchiomotor neurons, and by Rohon-Beard sensory neurons were also observed, which included truncation of axons and increased branching of motor axons. Moreover, agrin morphants exhibit significantly inhibited tail development in a dose-dependent manner, as well as defects in the formation of the midbrain-hindbrain boundary and reduced size of eyes and otic vesicles. Together these results show that agrin plays an important role in both peripheral and central nervous system development, and also modulates posterior development in zebrafish.