Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in the telencephalon
- Authors
- Hofmeister, W., Devine, C.A., Rothnagel, J.A., and Key, B.
- ID
- ZDB-PUB-120529-10
- Date
- 2012
- Source
- Mechanisms of Development 129(5-8): 109-124 (Journal)
- Registered Authors
- Key, Brian
- Keywords
- Frizzled-3, anterior commissure, post-optic commissure, slit2
- MeSH Terms
-
- Animals
- Axons/drug effects
- Axons/metabolism*
- Base Sequence
- Body Patterning/drug effects
- Body Patterning/genetics
- Diencephalon/cytology
- Diencephalon/drug effects
- Diencephalon/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Fertilization/drug effects
- Frizzled Receptors/genetics*
- Frizzled Receptors/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Gene Knockdown Techniques
- Intracellular Signaling Peptides and Proteins/genetics*
- Intracellular Signaling Peptides and Proteins/metabolism
- Models, Biological
- Molecular Sequence Data
- Morpholinos/pharmacology
- Neuroglia/drug effects
- Neuroglia/metabolism
- Phenotype
- Telencephalon/cytology
- Telencephalon/drug effects
- Telencephalon/embryology
- Telencephalon/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 22609481 Full text @ Mech. Dev.
The anterior commissure forms the first axon connections between the two sides of the embryonic telencephalon. We investigated the role of the transmembrane receptor Frizzled-3a in the development of this commissure using zebrafish as an experimental model. Knock down of Frizzled-3a resulted in complete loss of the anterior commissure. This defect was accompanied by a loss of the glial bridge, expansion of the slit2 expression domain and perturbation of the midline telencephalic–diencephalic boundary. Blocking Slit2 activity following knock down of Frizzled-3a effectively rescued the anterior commissure defect which suggested that Frizzled-3a was indirectly controlling the growth of axons across the rostral midline. We have shown here that Frizzled-3a is essential for normal development of the commissural plate and that loss-of-function causes Slit2-dependent defects in axon midline crossing in the embryonic vertebrate forebrain. These data supports a model whereby Wnt signaling through Frizzled-3a attenuates expression of Slit2 in the rostral midline of the forebrain. The absence of Slit2 facilitates the formation of a midline bridge of glial cells which is used as a substrate for commissural axons. In the absence of this platform of glia, commissural axons fail to cross the rostral midline of the forebrain.