Ccdc80-l1 Is Involved in Axon Pathfinding of Zebrafish Motoneurons

Chiara Brusegan,Isabella Della Noce,Anna Pistocchi,Andrea Frassine,Franco Cotelli,Filippo Schepis

doi:10.1371/journal.pone.0031851

Chiara Brusegan, Isabella Della Noce + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0031851

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Abstract

Axon pathfinding is a subfield of neural development by which neurons send out axons to reach the correct targets. In particular, motoneurons extend their axons toward skeletal muscles, leading to spontaneous motor activity. In this study, we identified the zebrafish Ccdc80 and Ccdc80-like1 (Ccdc80-l1) proteins in silico on the basis of their high aminoacidic sequence identity with the human CCDC80 (Coiled-Coil Domain Containing 80). We focused on ccdc80-l1 gene that is expressed in nervous and non-nervous tissues, in particular in territories correlated with axonal migration, such as adaxial cells and muscle pioneers. Loss of ccdc80-l1 in zebrafish embryos induced motility issues, although somitogenesis and myogenesis were not impaired. Our results strongly suggest that ccdc80-l1 is involved in axon guidance of primary and secondary motoneurons populations, but not in their proper formation. ccdc80-l1 has a differential role as regards the development of ventral and dorsal motoneurons, and this is consistent with the asymmetric distribution of the transcript. The axonal migration defects observed in ccdc80-l1 loss-of-function embryos are similar to the phenotype of several mutants with altered Hedgehog activity. Indeed, we reported that ccdc80-l1 expression is positively regulated by the Hedgehog pathway in adaxial cells and muscle pioneers. These findings strongly indicate ccdc80-l1 as a down-stream effector of the Hedgehog pathway.

Highlights

The development of a functional vertebrate nervous system requires elaboration of a large number of diverse cell types
Coiled-Coil-Domain Containing 80 (Ccdc80)-l1 is expressed in muscle pioneers and adaxial cells of the zebrafish embryo
At 24 hpf, ccdc80-l1 is detectable in a specific sub-population of migrating adaxial cells, that moves along the lateral axis towards the external somite [35] (Fig. 2E–G)

Summary

Introduction

The development of a functional vertebrate nervous system requires elaboration of a large number of diverse cell types. PMNs extend their axons out of the spinal cord at about 16–17 hpf, following a common pathway: their growth cones project ventrally along the medial surface of the myotome and pause at the horizontal myoseptum, which separates dorsal and ventral myotomes. They interact with muscle pioneers [6,7], a subset of two to six cells for each somite early differentiating into slow muscle fibers [8,9]. Secondary motoneurons (SMNs) growth cones extend later from spinal cord, beginning at 22 hpf and following the paths pioneered by the primary axons [11,12]

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