Wnt signalling in neuronal differentiation and development

Inestrosa, Nibaldo C.; Varela-Nallar, Lorena

doi:10.1007/s00441-014-1996-4

Cited by 130 publications

(96 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wnt signaling is known to play many important roles in the developing nervous system (reviewed by [227]); thus it will be important to determine whether altered Wnt signaling plays any role in the many neural functions identified for Pcdh proteins. Certainly, major disruption of Wnt signaling is incompatible with the formation of a structurally normal nervous system, so the discrete phenotypes observed when clustered or non-clustered Pcdhs are deleted in mice could only reflect fairly subtle modulation of Wnt pathways.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Wnt signaling by protocadherins

Mah

Weiner

2017

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

The ~70 protocadherins comprise the largest group within the cadherin superfamily. Their diversity, the complexity of the mechanisms through which their genes are regulated, and their many critical functions in nervous system development have engendered a growing interest in elucidating the intracellular signaling pathways through which they act. Recently, multiple protocadherins across several subfamilies have been implicated as modulators of Wnt signaling pathways, and through this as potential tumor suppressors. Here, we review the extant data on the regulation by protocadherins of Wnt signaling pathways and components, and highlight some key unanswered questions that could shape future research.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of Wnt signaling by protocadherins

Mah

Weiner

2017

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

show abstract

“…At the stage of the early germinal neuroepithelium, Wnt genes and Wnt pathway modulators are expressed in overlapping spatial and temporal patterns [62,63,64] and are critical for establishing signaling centers that inform regional identities along the rostral-caudal and dorsal-ventral axes of the developing CNS [65,66,67](Table 2). Structural and functional impairments in the forebrain (derived from telencephalon and diencephalon), midbrain (derived from mesencephalon), and hindbrain (derived from metencephalon and myelencephalon) have all been associated with neuropsychiatric pathogenesis [68,69,70].…”

Section: Brain Regionalizationmentioning

confidence: 99%

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

Mulligan

Cheyette

2016

Complex Psychiatry

View full text Add to dashboard Cite

Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions. Simultaneously, large-scale human genomic studies are providing evidence that sequence variation in Wnt signal pathway genes contributes to pathogenesis in several psychiatric disorders. This article reviews neurodevelopmental and postneurodevelopmental functions of Wnt signaling, highlighting mechanisms, whereby its disruption might contribute to psychiatric illness, and then reviews the most reliable recent genetic evidence supporting that mutations in Wnt pathway genes contribute to psychiatric illness. We are proponents of the notion that studies in animal and hiPSC models informed by the human genetic data combined with the deep knowledge base and tool kits generated over the last several decades of basic neurodevelopmental research will yield near-term tangible advances in neuropsychiatry.

show abstract

“…However, stabilized β-Cat was also shown to promote cortical progenitor differentiation (11). Thus, it has been proposed that Wnt/β-Cat signaling promotes proliferation and differentiation of cortical progenitors at early and late developmental stages, respectively (12). This raises the essential and largely open question of how Wnt/β-Cat regulates cortical progenitor proliferation and differentiation.…”

mentioning

confidence: 99%

Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis

Hsu

Nam

Cui

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The timing of cortical neurogenesis has a major effect on the size and organization of the mature cortex. The deletion of the LIMhomeodomain transcription factor Lhx2 in cortical progenitors by Nestin-cre leads to a dramatically smaller cortex. Here we report that Lhx2 regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis. The loss of Lhx2 in cortical progenitors results in precocious radial glia differentiation and a temporal shift of cortical neurogenesis. We further investigated the underlying mechanisms at play and demonstrated that in the absence of Lhx2, the Wnt/β-catenin pathway failed to maintain progenitor proliferation. We developed and applied a mathematical model that reveals how precocious neurogenesis affected cortical surface and thickness. Thus, we concluded that Lhx2 is required for β-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis.cortical neurogenesis | Lhx2 | β-catenin U nderstanding how genetic mechanisms interact to set up a precise developmental timing is a fundamental issue in biology. In the cerebral cortex, excitatory neurons are generated by progenitor cells in the dorsal telencephalon (dTel) lining the lateral ventricle. During the early developmental stages, cortical progenitors undergo symmetric divisions, resulting in the proliferation of progenitors and thereby allowing expansion of the developing cortex. Soon after, cortical progenitors start generating distinct types of neurons through asymmetric differentiative divisions (1-5). The precise timing of the switch from proliferative division to differentiative division is crucial to determining the number of cortical neurons, and thus the cortical size.The switch from proliferation to differentiation is reportedly regulated by the canonical Wnt signaling pathway, in which β-catenin (β-Cat) is the major downstream effector. In the absence of Wnt signaling, β-Cat is phosphorylated by glycogen synthase kinase 3 and targeted for proteosome degradation. Once Wnt ligands bind to the Frizzled-Lrp5/6 receptors, the activity of glycogen synthase kinase 3-Axin-APC (adenomatous polyposis coli) destruction complex is inhibited. As a consequence, β-Cat accumulates in the cytoplasm, translocates to the nucleus, and activates downstream gene transcription together with the lymphoid enhancer-binding factor (LEF)/ T-cell factor (TCF) transcription factors (6). Overexpression of the stabilized, N-terminally truncated form of β-Cat in cortical progenitors during early neurogenesis promotes their overproliferation (7,8), whereas inactivation of β-Cat in the cortex promotes neurogenesis (9, 10). However, stabilized β-Cat was also shown to promote cortical progenitor differentiation (11). Thus, it has been proposed that Wnt/β-Cat signaling promotes proliferation and differentiation of cortical progenitors at early and late developmental stages, respectively (12). This raises the essential and largely open question of ho...

show abstract

Wnt signalling in neuronal differentiation and development

Cited by 130 publications

References 106 publications

Regulation of Wnt signaling by protocadherins

Regulation of Wnt signaling by protocadherins

Neurodevelopmental Perspectives on Wnt Signaling in Psychiatry

Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis

Contact Info

Product

Resources

About