Dataset Information

Syntaphilin-Mediated Docking of Mitochondria at the Growth Cone Is Dispensable for Axon Elongation In Vivo.

ABSTRACT: Mitochondria are abundantly detected at the growth cone, the dynamic distal tip of developing axons that directs growth and guidance. It is, however, poorly understood how mitochondrial dynamics relate to growth cone behavior in vivo, and which mechanisms are responsible for anchoring mitochondria at the growth cone during axon pathfinding. Here, we show that in retinal axons elongating along the optic tract in zebrafish, mitochondria accumulate in the central area of the growth cone and are occasionally observed in filopodia extending from the growth cone periphery. Mitochondrial behavior at the growth cone in vivo is dynamic, with mitochondrial positioning and anterograde transport strongly correlating with growth cone behavior and axon outgrowth. Using novel zebrafish mutant lines that lack the mitochondrial anchoring proteins Syntaphilin a and b, we further show that Syntaphilins contribute to mitochondrial immobilization at the growth cone. Syntaphilins are, however, not required for proper growth cone morphology and axon growth in vivo, indicating that Syntaphilin-mediated anchoring of mitochondria at the growth cone plays only a minor role in elongating axons.

SUBMITTER: Verreet T

PROVIDER: S-EPMC6751374 | biostudies-literature | 2019 Sep/Oct

REPOSITORIES: biostudies-literature

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Publications

Syntaphilin-Mediated Docking of Mitochondria at the Growth Cone Is Dispensable for Axon Elongation <i>In Vivo</i>.

Verreet Tine T Weaver Cory J CJ Hino Hiromu H Hibi Masahiko M Poulain Fabienne E FE

eNeuro 20190918 5

Mitochondria are abundantly detected at the growth cone, the dynamic distal tip of developing axons that directs growth and guidance. It is, however, poorly understood how mitochondrial dynamics relate to growth cone behavior <i>in vivo</i>, and which mechanisms are responsible for anchoring mitochondria at the growth cone during axon pathfinding. Here, we show that in retinal axons elongating along the optic tract in zebrafish, mitochondria accumulate in the central area of the growth cone and ...[more]

PMID: 31481398

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Project description:BackgroundHow axon guidance signals regulate growth cone behavior and guidance decisions in the complex in vivo environment of the central nervous system is not well understood. We have taken advantage of the unique features of the zebrafish embryo to visualize dynamic growth cone behaviors and analyze guidance mechanisms of axons emerging from a central brain nucleus in vivo.ResultsWe investigated axons of the nucleus of the medial longitudinal fascicle (nucMLF), which are the first axons to extend in the zebrafish midbrain. Using in vivo time-lapse imaging, we show that both positive axon-axon interactions and guidance by surrounding tissue control initial nucMLF axon guidance. We further show that two guidance molecules, transient axonal glycoprotein-1 (TAG-1) and laminin-alpha1, are essential for the initial directional extension of nucMLF axons and their subsequent convergence into a tight fascicle. Fixed tissue analysis shows that TAG-1 knockdown causes errors in nucMLF axon pathfinding similar to those seen in a laminin-alpha1 mutant. However, in vivo time-lapse imaging reveals that while some defects in dynamic growth cone behavior are similar, there are also defects unique to the loss of each gene. Loss of either TAG-1 or laminin-alpha1 causes nucMLF axons to extend into surrounding tissue in incorrect directions and reduces axonal growth rate, resulting in stunted nucMLF axons that fail to extend beyond the hindbrain. However, defects in axon-axon interactions were found only after TAG-1 knockdown, while defects in initial nucMLF axon polarity and excessive branching of nucMLF axons occurred only in laminin-alpha1 mutants.ConclusionThese results demonstrate how two guidance cues, TAG-1 and laminin-alpha1, influence the behavior of growth cones during axon pathfinding in vivo. Our data suggest that TAG-1 functions to allow growth cones to sense environmental cues and mediates positive axon-axon interactions. Laminin-alpha1 does not regulate axon-axon interactions, but does influence neuronal polarity and directional guidance.

Dataset Information

Syntaphilin-Mediated Docking of Mitochondria at the Growth Cone Is Dispensable for Axon Elongation In Vivo.

Publications

Syntaphilin-Mediated Docking of Mitochondria at the Growth Cone Is Dispensable for Axon Elongation <i>In Vivo</i>.

Similar Datasets

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