A Zic2-regulated switch in a noncanonical Wnt/ßcatenin pathway is essential for the formation of bilateral circuits.
Por:
Morenilla-Palao C, López-Cascales MT, López-Atalaya JP, Baeza D, Calvo-Díaz L, Barco A and Herrera E
Publicada:
13 nov 2020
Ahead of Print:
13 nov 2020
Resumen:
The Wnt pathway is involved in a wide array of biological processes during development and is deregulated in many pathological scenarios. In neurons, Wnt proteins promote both axon extension and repulsion, but the molecular mechanisms underlying these opposing axonal responses are unknown. Here, we show that Wnt5a is expressed at the optic chiasm midline and promotes the crossing of retinal axons by triggering an alternative Wnt pathway that depends on the accumulation of ßcatenin but does not activate the canonical pathway. In ipsilateral neurons, the transcription factor Zic2 switches this alternative Wnt pathway by regulating the expression of a set of Wnt receptors and intracellular proteins. In combination with this alternative Wnt pathway, the asymmetric activation of EphB1 receptors at the midline phosphorylates ßcatenin and elicits a repulsive response. This alternative Wnt pathway and its Zic2-triggered switch may operate in other contexts that require a two-way response to Wnt ligands.
Filiaciones:
:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain
López-Cascales MT:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain
López-Atalaya JP:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain
:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain
Calvo-Díaz L:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain
Barco A:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain
Herrera E:
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández (CSIC-UMH), Campus San Juan, Av. Ramón y Cajal s/n, Alicante 03550, Spain.
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