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ZIRC
ZFIN ID: ZDB-PUB-120529-10
Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in the telencephalon
Hofmeister, W., Devine, C.A., Rothnagel, J.A., and Key, B.
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.
ABSTRACT

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.

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