TY - JOUR
T1 - Wnt Signaling Directs Neuronal Polarity and Axonal Growth
AU - Stanganello, Eliana
AU - Zahavi, Eitan Erez
AU - Burute, Mithila
AU - Smits, Jasper
AU - Jordens, Ingrid
AU - Maurice, Madelon M.
AU - Kapitein, Lukas C.
AU - Hoogenraad, Casper C.
N1 - Funding Information:
We thank Dr. Gary Davidson for sharing the Lrp6-GFP construct. This work was supported by the Netherlands Organisation for Health Research and Development (ZonMW-TOP, 912.16.058 to CCH, and VICI grant 91815604 and ECHO grant 711.013.012 to MMM), the European Research Council (ERC) (ERC-consolidator, 617050, CCH) and European Molecular Biology Organization ( 1184-2015 EMBO-ALTF, ES). The work contributed by M.M.M. and I.J. is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society .
Funding Information:
We thank Dr. Gary Davidson for sharing the Lrp6-GFP construct. This work was supported by the Netherlands Organisation for Health Research and Development (ZonMW-TOP, 912.16.058 to CCH, and VICI grant 91815604 and ECHO grant 711.013.012 to MMM), the European Research Council (ERC)(ERC-consolidator, 617050, CCH)and European Molecular Biology Organization (1184-2015 EMBO-ALTF, ES). The work contributed by M.M.M. and I.J. is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. E.S. designed the project, performed all experiments, and wrote the manuscript; E.E.Z. and J.S. contributed to the MFC experiments and the revision of the paper; M.B. contributed to the micropattern experiments; M.M.M. and I.J. provided essential reagents, assays, and constructs; L.C.K. supervised the MFC experiments; C.C.H. supervised the project. The authors declare no competing interests.
Publisher Copyright:
© 2019 The Authors
PY - 2019/3/29
Y1 - 2019/3/29
N2 - The establishment of neuronal polarity is driven by cytoskeletal remodeling that stabilizes and promotes the growth of a single axon from one of the multiple neurites. The importance of the local microtubule stabilization in this process has been revealed however, the external signals initiating the cytoskeletal rearrangements are not completely understood. In this study, we show that local activation of the canonical Wnt pathway regulates neuronal polarity and axonal outgrowth. We found that in the early stages of neuronal polarization, Wnt3a accumulates in one of the neurites of unpolarized cells and thereby could determine axon positioning. Subsequently, Wnt3a localizes to the growing axon, where it activates the canonical Wnt pathway and controls axon positioning and axonal length. We propose a model in which Wnt3a regulates the formation and growth of the axon by activating local intracellular signaling events leading to microtubule remodeling.
AB - The establishment of neuronal polarity is driven by cytoskeletal remodeling that stabilizes and promotes the growth of a single axon from one of the multiple neurites. The importance of the local microtubule stabilization in this process has been revealed however, the external signals initiating the cytoskeletal rearrangements are not completely understood. In this study, we show that local activation of the canonical Wnt pathway regulates neuronal polarity and axonal outgrowth. We found that in the early stages of neuronal polarization, Wnt3a accumulates in one of the neurites of unpolarized cells and thereby could determine axon positioning. Subsequently, Wnt3a localizes to the growing axon, where it activates the canonical Wnt pathway and controls axon positioning and axonal length. We propose a model in which Wnt3a regulates the formation and growth of the axon by activating local intracellular signaling events leading to microtubule remodeling.
KW - Cellular Neuroscience
KW - Molecular Neuroscience
KW - Neuroscience
UR - https://www.scopus.com/pages/publications/85066233546
U2 - 10.1016/j.isci.2019.02.029
DO - 10.1016/j.isci.2019.02.029
M3 - Article
C2 - 30878878
AN - SCOPUS:85066233546
VL - 13
SP - 318
EP - 327
JO - iScience
JF - iScience
ER -