15-07-08(19:13:31)

Authors:

Kastenhuber E 1; Schweitzer J 1; Kratochwil C 1; Kern U 1; Ryu S 1,2; Driever W 1

Institutions:

1 Developmental Biology, Faculty of Biology, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany
2 present address: Max Planck Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany

Title of abstract : Establishment of catecholaminergic circuitry in the zebrafish

Abstract text:

The transparent zebrafish embryo provides an ideal system to study establishment of CA circuitry, as most catecholaminergic (CA) neuronal groups form during the first four days of development. Specific dopaminergic (DA) subgroups of the ventral diencephalon are connected to subpallium, pretectum, hypothalamus, pre-optic region, or project caudally along the longitudinal catecholaminergic bundle (LCB) into hindbrain and spinal cord. The mechanisms guiding CA axons are not well understood.

Using genetic ablation of defined CA groups, we found that posterior tubercular DA neurons provide the majority of axons of the LCB. The projection path of the LCB does not correlate with the medial or lateral longitudinal fascicle of the primary axonal scaffold, indicating that mediolateral positioning of CA tracts is determined independent of the earlier developing scaffold. We found that the Slit receptor Robo2 and the Netrin receptor Dcc are coexpressed in diencephalic DA neurons with descending projections. In astray (robo2-/-) embryos axons of the LCB grow in close proximity to the midline, leaving their normal lateral position. This phenotype can be rescued when the attractive signal from the midline is knocked down by injection of dcc or ntn1 morpholinos.

Our results show that Netrin/Dcc and Robo/Slit signaling interact to define the lateral position of hindbrain longitudinal CA tracts. The attractive Netrin signal appears to counteract the repulsive Slit signal. We thus demonstrate that, in vertebrates, attractive and repulsive cues cooperate to specify lateral positions of CA longitudinal axon tracts in the hindbrain.


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