Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling

Lyuksyutova, Anna I; Lu, Chin Chun; Milanesio, Nancy; King, Leslie A.; Guo, Nini; Wang, Yanshu; Nathans, Jeremy; Tessier‐Lavigne, Marc; Zou, Yimin

doi:10.1126/science.1089610

Cited by 522 publications

(563 citation statements)

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“…Knocking down Celsr2 expression reduces the length of apical dendrites and the numbers of basal Celsr3 mutant mice have defects in several major axonal tracts, a phenotype similar to that of Fzd3 mutant mice [38,39] . In both mutants, commissural spinal cord axons fail to turn rostrally after crossing the midline [40][41][42] ; thalamocortical, corticofugal and subcerebral axons are unable to traverse the ventral telencephalon to reach their targets, and the development of some commissures is defective.…”

Section: Two Mouse Mutants Of Celsr1 Have Been Identified Inmentioning

confidence: 99%

Planar cell polarity genes, Celsr1-3, in neural development

2012

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flamingo is among the 'core' planar cell-polarity genes, protein of which belongs to a unique cadherin subfamily.In contrast to the classic cadherins, composed of several extracellular cadherin repeats, one transmembrane domain and one cytoplasmic segment linked to catenin binding, Drosophila Flamingo has seven transmembrane segments and a cytoplasmic tail with no catenin-binding sequence. In Drosophila, Flamingo has pleotropic roles in controlling epithelial polarity and neuronal morphogenesis. Three mammalian orthologs of flamingo, Celsr1-3, are widely expressed in the nervous system. Recent work has shown that Celsr1-3 play important roles in neural development, such as in axon guidance, neuronal migration, and cilium polarity. Celsr1-3 single-gene knockout mice exhibit different phenotypes, but there are cooperative interactions among these genes.

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Section: Two Mouse Mutants Of Celsr1 Have Been Identified Inmentioning

confidence: 99%

Planar cell polarity genes, Celsr1-3, in neural development

2012

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“…For instance, both Wnt4 and wnt5a are chemoattractants for mouse spinal commissural axons (Lyuksyutova et al, 2003;Shafer et al, 2011). After crossing the ventral midline these axons have been proposed to respond directly to gradients of Wnt4 and Wnt5a which cause them to ascend the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

“…After crossing the ventral midline these axons have been proposed to respond directly to gradients of Wnt4 and Wnt5a which cause them to ascend the spinal cord. Interestingly, the response of an axon to a particular Wnt ligand is context dependent since Wnt5a can act either as a chemorepellent (Liu et al, 2005;Fenstermaker et al, 2010;Blakely et al, 2011) or as a chemoattractant (Lyuksyutova et al, 2003;Fenstermaker et al, 2010;Shafer et al, 2011) for different neuronal populations.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of function studies in mouse and fish have linked Fzd3 to the planar cell polarity pathway (Wang et al, 2002;Lyuksyutova et al, 2003;Wada et al, 2006;Wang et al, 2006a;Wang et al, 2006b). In vitro studies indicate that mFzd3 can cause an increase in intracellular Ca 2+ levels (Slusarski et al, 1997a;Slusarski et al, 1997b;Liu et al, 1999;Kuhl et al, 2000;Sheldahl et al, 2003;), thereby implicating the Wnt/Ca 2+ signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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Frizzled-3a and Wnt-8b genetically interact during forebrain commissural formation in embryonic zebrafish

Hofmeister

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2013

Brain Research

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Number of words: 3225Key words: Wnt8b, Fzd3a, axon guidance, commissure, zebrafish, slit2Keyfindings:• Knockdown of Wnt8b results in an absence of the anterior commissure and a reduction of the post-optic commissure • Knockdown of Wnt8b results in a expansion of slit2 at the rostral midline and a reduction of the glial bridge • The phenotype observed following knockdown of Wnt8b is similar to that seen following knockdown of Fzd3a • Combined loss of both Wnt8b and Fzd3a caused a synergistic increase in commissural defects and abnormal slit2 expression • Fzd3a and Wnt8b act in the same genetic pathway to control normal patterning of the commissural plate Acknowledgements: This work was supported by grants from NHMRC and ARC to B.K.2 AbstractThe commissural plate forms the rostral surface of the embryonic vertebrate forebrain and provides a cellular substrate for forebrain commissural axons. We have previously reported that the Wnt receptor frizzled-3a (fzd3a) restricts the expression of the chemorepulsive guidance ligand slit2 to a discrete domain of neuroepithelial cells in the commissural plate of embryonic zebrafish. Loss-of-Fzd3a function perturbed slit2 expression and disrupted the formation of glial bridges which guide the formation of forebrain commissures. We now show that Wnt8b is also necessary for anterior commissural formation as well as for patterning of slit2 expression at the midline. Knock down of Wnt8b produced the same phenotype as loss of Fzd3a which suggested that these genes were acting together to regulate axon guidance. Simultaneous sub-threshold knock down of both Fzd3a and Wnt8b led to a greater than additive increase in the penetrance of the mutant phenotype which indicated that these two genes were indeed interacting. We have shown here that Fzd3a/Wnt8b signaling is essential for normal patterning of the commissural plate and that loss-of-function in either receptor or ligand causes Slit2-dependent defects in glial bridge morphology which indirectly attenuated axon midline crossing in the embryonic vertebrate forebrain.3

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“…(Figure 1). Chez la souris, un gradient caudo-rostral de Wnt-4 agit comme facteur chimioattracteur pour les axones commissuraux ayant traversé la plaque basale [6], tandis que chez le poulet, un gradient rostro-caudal de Shh agit comme facteur chimiorépulsif pour les axones commissuraux ayant traversé [7]. Bien qu'il n'ait pas été démontré que ce gradient rostrocaudal de Shh existe chez la souris, il sera intéressant de tester si Boc est requis pour le guidage des axones des neurones commissuraux selon l'axe rostro-caudal.…”

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