A Zic2-regulated Switch in a Noncanonical Wnt/βcatenin Pathway is Essential for the Formation of Bilateral Circuits

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Nov 14

PMID 33188033

Citations 14

Authors

Cruz Morenilla-Palao

Maria Teresa Lopez-Cascales

Jose P Lopez-Atalaya

Diana Baeza

Luis Calvo-Diaz

Angel Barco

Eloisa Herrera

Affiliations

Soon will be listed here.

Abstract

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 βcatenin 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 βcatenin 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.

Citing Articles

ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification.

Barnada S, Giner de Gracia A, Morenilla-Palao C, Lopez-Cascales M, Scopa C, Waltrich Jr F Am J Hum Genet. 2024; 111(10):2232-2252.

PMID: 39226899 PMC: 11480806. DOI: 10.1016/j.ajhg.2024.07.022.

Proper Frequency of Perinatal Retinal Waves Is Essential for the Precise Wiring of Visual Axons in Nonimage-Forming Nuclei.

Negueruela S, Morenilla-Palao C, Sala S, Ordono P, Herrera M, Coca Y J Neurosci. 2024; 44(40).

PMID: 39151955 PMC: 11450533. DOI: 10.1523/JNEUROSCI.1408-23.2024.

Repurposing development genes for axonal regeneration following injury: Examining the roles of Wnt signaling.

Albano G, Hackam A Front Cell Dev Biol. 2024; 12:1417928.

PMID: 38882059 PMC: 11176474. DOI: 10.3389/fcell.2024.1417928.

Cables1 links Slit/Robo and Wnt/Frizzled signaling in commissural axon guidance.

Zuniga N, Dumoulin A, Vaccaro G, Stoeckli E Development. 2023; 150(19).

PMID: 37747104 PMC: 10617602. DOI: 10.1242/dev.201671.

Neurogenesis redirects β-catenin from adherens junctions to the nucleus to promote axonal growth.

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PMID: 37519286 PMC: 10482005. DOI: 10.1242/dev.201651.

References

Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

Fenstermaker A, Prasad A, Bechara A, Adolfs Y, Tissir F, Goffinet A . Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J Neurosci. 2010; 30(47):16053-64. PMC: 3073573. DOI: 10.1523/JNEUROSCI.4508-10.2010. View

Herrera E, Brown L, Aruga J, Rachel R, Dolen G, Mikoshiba K . Zic2 patterns binocular vision by specifying the uncrossed retinal projection. Cell. 2003; 114(5):545-57. DOI: 10.1016/s0092-8674(03)00684-6. View

Shafer B, Onishi K, Lo C, Colakoglu G, Zou Y . Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance. Dev Cell. 2011; 20(2):177-91. PMC: 3235522. DOI: 10.1016/j.devcel.2011.01.002. View

Nagai T, Aruga J, Minowa O, Sugimoto T, Ohno Y, Noda T . Zic2 regulates the kinetics of neurulation. Proc Natl Acad Sci U S A. 2000; 97(4):1618-23. PMC: 26484. DOI: 10.1073/pnas.97.4.1618. View

Herrera E, Erskine L, Morenilla-Palao C . Guidance of retinal axons in mammals. Semin Cell Dev Biol. 2017; 85:48-59. DOI: 10.1016/j.semcdb.2017.11.027. View

Houtmeyers R, Souopgui J, Tejpar S . Deregulation of ZIC Family Members in Oncogenesis. Adv Exp Med Biol. 2018; 1046:329-338. DOI: 10.1007/978-981-10-7311-3_16. View

Valenta T, Hausmann G, Basler K . The many faces and functions of β-catenin. EMBO J. 2012; 31(12):2714-36. PMC: 3380220. DOI: 10.1038/emboj.2012.150. View

Pourebrahim R, Houtmeyers R, Ghogomu S, Janssens S, Thelie A, Tran H . Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling. J Biol Chem. 2011; 286(43):37732-40. PMC: 3199516. DOI: 10.1074/jbc.M111.242826. View

10.

Rabadan M, Herrera A, Fanlo L, Usieto S, Carmona-Fontaine C, Barriga E . Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2. Development. 2016; 143(12):2194-205. PMC: 4920176. DOI: 10.1242/dev.134981. View

11.

Houtmeyers R, Tchouate Gainkam O, Glanville-Jones H, Van den Bosch B, Chappell A, Barratt K . Zic2 mutation causes holoprosencephaly via disruption of NODAL signalling. Hum Mol Genet. 2016; 25(18):3946-3959. DOI: 10.1093/hmg/ddw235. View

12.

Garcia-Frigola C, Carreres M, Vegar C, Mason C, Herrera E . Zic2 promotes axonal divergence at the optic chiasm midline by EphB1-dependent and -independent mechanisms. Development. 2008; 135(10):1833-41. DOI: 10.1242/dev.020693. View

13.

Yoshikawa S, McKinnon R, Kokel M, Thomas J . Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature. 2003; 422(6932):583-8. DOI: 10.1038/nature01522. View

14.

Fernandez-Nogales M, Murcia-Belmonte V, Chen H, Herrera E . The peripheral eye: A neurogenic area with potential to treat retinal pathologies?. Prog Retin Eye Res. 2018; 68:110-123. PMC: 7654208. DOI: 10.1016/j.preteyeres.2018.09.001. View

15.

Chai G, Zhou L, Manto M, Helmbacher F, Clotman F, Goffinet A . Celsr3 is required in motor neurons to steer their axons in the hindlimb. Nat Neurosci. 2014; 17(9):1171-9. DOI: 10.1038/nn.3784. View

16.

Kuwajima T, Soares C, Sitko A, Lefebvre V, Mason C . SoxC Transcription Factors Promote Contralateral Retinal Ganglion Cell Differentiation and Axon Guidance in the Mouse Visual System. Neuron. 2017; 93(5):1110-1125.e5. PMC: 5346053. DOI: 10.1016/j.neuron.2017.01.029. View

17.

Garcia-Frigola C, Carreres M, Vegar C, Herrera E . Gene delivery into mouse retinal ganglion cells by in utero electroporation. BMC Dev Biol. 2007; 7:103. PMC: 2080638. DOI: 10.1186/1471-213X-7-103. View

18.

McCrea P, Turck C, Gumbiner B . A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991; 254(5036):1359-61. DOI: 10.1126/science.1962194. View

19.

Fradkin L, Noordermeer J, Nusse R . The Drosophila Wnt protein DWnt-3 is a secreted glycoprotein localized on the axon tracts of the embryonic CNS. Dev Biol. 1995; 168(1):202-13. DOI: 10.1006/dbio.1995.1072. View

20.

Chedotal A . Roles of axon guidance molecules in neuronal wiring in the developing spinal cord. Nat Rev Neurosci. 2019; 20(7):380-396. DOI: 10.1038/s41583-019-0168-7. View