Wnt signalling in neuronal differentiation and development
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Wnts are secreted glycoproteins that play multiple roles in early development, including the differentiation of precursor cells. During this period, gradients of Wnts and other morphogens are formed and regulate the differentiation and migration of neural progenitor cells. Afterwards, Wnt signalling cascades participate in the formation of neuronal circuits, playing roles in dendrite and axon development, dendritic spine formation and synaptogenesis. Finally, in the adult brain, Wnts control hippocampal plasticity, regulating synaptic transmission and neurogenesis. In this review, we summarize the reported roles of Wnt signalling cascades in these processes with a particular emphasis on the role of Wnts in neuronal differentiation and development.
KeywordsWnt signalling pathway Neural progenitor cells Neuronal differentiation Neuronal maturation Adult neurogenesis
We thank Felipe G. Serrano (CARE, Department of Cell and Molecular Biology, P. Catholic University of Chile) for artwork. This work was supported by Grants from FONDECYT (No. 1120156) and the Basal Center of Excellence in Science and Technology (CONICYT-PFB12/2007) to N.C.I. and by a Grant from FONDECYT (No. 11110012) to L.V.-N.
- Arrazola MS, Varela-Nallar L, Colombres M, Toledo EM, Cruzat F, Pavez L, Assar R, Aravena A, Gonzalez M, Montecino M, Maass A, Martinez S, Inestrosa NC (2009) Calcium/calmodulin-dependent protein kinase type IV is a target gene of the Wnt/beta-catenin signaling pathway. J Cell Physiol 221:658–667PubMedGoogle Scholar
- Bielen H, Houart C (2014) The Wnt cries many: Wnt regulation of neurogenesis through tissue patterning, proliferation, and asymmetric cell division. Neurobiol Dev (in press)Google Scholar
- Carter M, Chen X, Slowinska B, Minnerath S, Glickstein S, Shi L, Campagne F, Weinstein H, Ross ME (2005) Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6. Proc Natl Acad Sci U S A 102:12843–12848PubMedCentralPubMedGoogle Scholar
- Ciani L, Boyle KA, Dickins E, Sahores M, Anane D, Lopes DM, Gibb AJ, Salinas PC (2011) Wnt7a signaling promotes dendritic spine growth and synaptic strength through Ca2+/Calmodulin-dependent protein kinase II. Proc Natl Acad Sci U S A 108:10732–10737Google Scholar
- Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B, Copp AJ, Henderson DJ, Spurr N, Stanier P, Fisher EM, Nolan PM, Steel KP, Brown SD, Gray IC, Murdoch JN (2003) Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol 13:1129–1133PubMedGoogle Scholar
- Jang MH, Bonaguidi MA, Kitabatake Y, Sun J, Song J, Kang E, Jun H, Zhong C, Su Y, Guo JU, Wang MX, Sailor KA, Kim JY, Gao Y, Christian KM, Ming GL, Song H (2013) Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell 12:215–223PubMedCentralPubMedGoogle Scholar
- Karalay O, Doberauer K, Vadodaria KC, Knobloch M, Berti L, Miquelajauregui A, Schwark M, Jagasia R, Taketo MM, Tarabykin V, Lie DC, Jessberger S (2011) Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis. Proc Natl Acad Sci U S A 108:5807–5812PubMedCentralPubMedGoogle Scholar
- Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK, Tassa C, Berry EM, Soda T, Singh KK, Biechele T, Petryshen TL, Moon RT, Haggarty SJ, Tsai LH (2009) Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell 136:1017–1031PubMedCentralPubMedGoogle Scholar
- Qu Q, Sun G, Li W, Yang S, Ye P, Zhao C, Yu RT, Gage FH, Evans RM, Shi Y (2010) Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal. Nat Cell Biol 12:31-40; sup pp 31-39Google Scholar
- Varela-Nallar L, Aranguiz FC, Abbott AC, Slater PG, Inestrosa NC (2010b) Adult hippocampal neurogenesis in aging and Alzheimer’s disease. Birth Defects Res C 90:284–296Google Scholar
- Varela-Nallar L, Rojas-Abalos M, Abbott AC, Moya EA, Iturriaga R, Inestrosa NC (2014) Chronic hypoxia induces the activation of the Wnt/beta-catenin signaling pathway and stimulates hippocampal neurogenesis in wild-type and APPswe-PS1DeltaE9 transgenic mice in vivo. Front Cell Neurosci 8:17PubMedCentralPubMedGoogle Scholar