Dataset Information

Rab33a and Rab33ba mediate the outgrowth of forebrain commissural axons in the zebrafish brain.

ABSTRACT: Rab small GTPases play key roles in intracellular membrane trafficking. Rab33a promotes axon outgrowth of cultured rat hippocampal neurons by mediating the anterograde axonal transport of Golgi-derived vesicles and the concomitant exocytosis of these vesicles at the growth cone. However, the functions of Rab33 in vivo are unclear. Here, we show that zebrafish rab33a and rab33ba are orthologs of mammalian Rab33a and Rab33b, respectively. They are expressed in the developing brain, including in neurons of the telencephalic dorsorostral cluster and the diencephalic ventrorostral cluster, which project axons to form the anterior and postoptic commissures, respectively. Although rab33a single mutant and rab33ba single mutant fish did not show remarkable defects, fish carrying the rab33a;rab33ba double mutations displayed dysgenesis of the anterior and postoptic commissures. Single-cell labeling in the telencephalic dorsorostral cluster demonstrated that the rab33a;rab33ba double mutation inhibits axonal extension in the anterior commissure. These results suggest that Rab33a and Rab33ba mediate axon outgrowth and the formation of the forebrain commissures in the zebrafish brain in a cooperative manner.

SUBMITTER: Huang L

PROVIDER: S-EPMC6372587 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Rab33a and Rab33ba mediate the outgrowth of forebrain commissural axons in the zebrafish brain.

Huang Liguo L Urasaki Akihiro A Inagaki Naoyuki N

Scientific reports 20190212 1

Rab small GTPases play key roles in intracellular membrane trafficking. Rab33a promotes axon outgrowth of cultured rat hippocampal neurons by mediating the anterograde axonal transport of Golgi-derived vesicles and the concomitant exocytosis of these vesicles at the growth cone. However, the functions of Rab33 in vivo are unclear. Here, we show that zebrafish rab33a and rab33ba are orthologs of mammalian Rab33a and Rab33b, respectively. They are expressed in the developing brain, including in ne ...[more]

PMID: 30755680

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Project description:BackgroundLong-distance axonal growth relies on the precise interplay of guidance cues and cell adhesion molecules. While guidance cues provide positional and directional information for the advancing growth cone, cell adhesion molecules are essential in enabling axonal advancement. Such a dependence on adhesion as well as guidance molecules can be well observed in dorsal commissural interneurons, which follow a highly stereotypical growth and guidance pattern. The mechanisms and molecules involved in the attraction and outgrowth towards the ventral midline, the axon crossing towards the contralateral side, the rostral turning after midline crossing as well as the guidance along the longitudinal axis have been intensely studied. However, little is known about molecules that provide the basis for commissural axon growth along the anterior-posterior axis.ResultsMDGA2, a recently discovered cell adhesion molecule of the IgCAM superfamily, is highly expressed in dorsolaterally located (dI1) spinal interneurons. Functional studies inactivating MDGA2 by RNA interference (RNAi) or function-blocking antibodies demonstrate that either treatment results in a lack of commissural axon growth along the longitudinal axis. Moreover, results from RNAi experiments targeting the contralateral side together with binding studies suggest that homophilic MDGA2 interactions between ipsilaterally projecting axons and post-crossing commissural axons may be the basis of axonal growth along the longitudinal axis.ConclusionsDirected axonal growth of dorsal commissural interneurons requires an elaborate mixture of instructive (guidance) and permissive (outgrowth supporting) molecules. While Wnt and Sonic hedgehog (Shh) signalling pathways have been shown to specify the growth direction of post-crossing commissural axons, our study now provides evidence that homophilic MDGA2 interactions are essential for axonal extension along the longitudinal axis. Interestingly, so far each part of the complex axonal trajectory of commissural axons uses its own set of guidance and growth-promoting molecules, possibly explaining why such a high number of molecules influencing the growth pattern of commissural interneurons has been identified.

Dataset Information

Rab33a and Rab33ba mediate the outgrowth of forebrain commissural axons in the zebrafish brain.

Publications

Rab33a and Rab33ba mediate the outgrowth of forebrain commissural axons in the zebrafish brain.

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