The Wnt-activated Xiro1 gene encodes a repressor that is essential for neural development and downregulates Bmp4

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 551-560 ◽  
Author(s):  
J. Gomez-Skarmeta ◽  
E. de La Calle-Mustienes ◽  
J. Modolell
Keyword(s):  
Wnt Signaling ◽  
Neural Development ◽  
Neural Differentiation ◽  
Neural Plate ◽  
Xenopus Embryo ◽  
Homeodomain Proteins ◽  
Proneural Genes ◽  
Family Control

In the early Xenopus embryo, the Xiro homeodomain proteins of the Iroquois (Iro) family control the expression of proneural genes and the size of the neural plate. We report that Xiro1 functions as a repressor that is strictly required for neural differentiation, even when the BMP4 pathway is impaired. We also show that Xiro1 and Bmp4 repress each other. Consistently, Xiro1 and Bmp4 have complementary patterns of expression during gastrulation. The expression of Xiro1 requires Wnt signaling. Thus, Xiro1 is probably a mediator of the known downregulation of Bmp4 by Wnt signaling.

How Wnt Signaling Builds the Brain: Bridging Development and Disease

2016 ◽  
Vol 23 (3) ◽  
pp. 314-329 ◽  
Author(s):  
Rivka Noelanders ◽  
Kris Vleminckx
Keyword(s):  
Wnt Signaling ◽  
Neural Development ◽  
Neurological Disorders ◽  
Neural Differentiation ◽  
Neurological Diseases ◽  
Physiological Role ◽  
Adult Brain ◽  
Neurological Dysfunction ◽  
The Brain

Wnt/β-catenin signaling plays a crucial role throughout all stages of brain development and remains important in the adult brain. Accordingly, many neurological disorders have been linked to Wnt signaling. Defects in Wnt signaling during neural development can give rise to birth defects or lead to neurological dysfunction later in life. Developmental signaling events can also be hijacked in the adult and result in disease. Moreover, knowledge about the physiological role of Wnt signaling in the brain might lead to new therapeutic strategies for neurological diseases. Especially, the important role for Wnt signaling in neural differentiation of pluripotent stem cells has received much attention as this might provide a cure for neurodegenerative disorders. In this review, we summarize the versatile role of Wnt/β-catenin signaling during neural development and discuss some recent studies linking Wnt signaling to neurological disorders.

scholarly journals ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

2019 ◽  
Author(s):  
Xiaoyun Sun ◽  
Xixia Peng ◽  
Yuqing Cao ◽  
Yan Zhou ◽  
Yuhua Sun
Keyword(s):  
Wnt Signaling ◽  
Neural Development ◽  
Neural Differentiation ◽  
Developmental Disorders ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Neural Induction ◽  
Neuron Death ◽  
Aberrant Expression ◽  
Protein Levels

AbstractADNP (Activity Dependent Neuroprotective Protein) is proposed as a neuroprotective protein whose aberrant expression has been frequently linked to neural developmental disorders, including the Helsmoortel-Van der Aa syndrome. However, its role in neural development and pathology remains unclear. Using mESC (mouse embryonic stem cell) directional neural differentiation as a model, we show that ADNP is required for ESC neural induction and neuronal differentiation by maintaining Wnt signaling. Mechanistically, ADNP functions to maintain the proper protein levels of β-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex: Axin and APC. Loss of ADNP promotes the formation of the degradation complex and hyperphosphorylation of β-Catenin by GSK3β and subsequent degradation via ubiquitin-proteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. We further show that ADNP plays key role in cerebellar neuron formation. Finally, adnp gene disruption in zebrafish embryos recapitulates key features of the mouse phenotype, including the reduced Wnt signaling, defective embryonic cerebral neuron formation and the massive neuron death. Thus, our work provides important insights into the role of ADNP in neural development and the pathology of the Helsmoortel-Van der Aa syndrome caused by ADNP gene mutation.

scholarly journals Comparison of plasma and cerebrospinal fluid proteomes identifies gene products guiding adult neurogenesis and neural differentiation in birds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eleni Voukali ◽  
Nithya Kuttiyarthu Veetil ◽  
Pavel Němec ◽  
Pavel Stopka ◽  
Michal Vinkler
Keyword(s):  
Cerebrospinal Fluid ◽  
Adult Neurogenesis ◽  
Neural Development ◽  
Neural Differentiation ◽  
Csf Proteins ◽  
Nymphicus Hollandicus ◽  
Liquid Chromatography Tandem Mass ◽  
Genome Information ◽  
Insight Into ◽  
Brain Homeostasis

AbstractCerebrospinal fluid (CSF) proteins regulate neurogenesis, brain homeostasis and participate in signalling during neuroinflammation. Even though birds represent valuable models for constitutive adult neurogenesis, current proteomic studies of the avian CSF are limited to chicken embryos. Here we use liquid chromatography–tandem mass spectrometry (nLC-MS/MS) to explore the proteomic composition of CSF and plasma in adult chickens (Gallus gallus) and evolutionarily derived parrots: budgerigar (Melopsittacus undulatus) and cockatiel (Nymphicus hollandicus). Because cockatiel lacks a complete genome information, we compared the cross-species protein identifications using the reference proteomes of three model avian species: chicken, budgerigar and zebra finch (Taeniopygia guttata) and found the highest identification rates when mapping against the phylogenetically closest species, the budgerigar. In total, we identified 483, 641 and 458 unique proteins consistently represented in the CSF and plasma of all chicken, budgerigar and cockatiel conspecifics, respectively. Comparative pathways analyses of CSF and blood plasma then indicated clusters of proteins involved in neurogenesis, neural development and neural differentiation overrepresented in CSF in each species. This study provides the first insight into the proteomics of adult avian CSF and plasma and brings novel evidence supporting the adult neurogenesis in birds.

scholarly journals Nemo-Like Kinase-Myocyte Enhancer Factor 2A Signaling Regulates Anterior Formation in Xenopus Development

2007 ◽  
Vol 27 (21) ◽  
pp. 7623-7630 ◽  
Author(s):  
Kiyotoshi Satoh ◽  
Junji Ohnishi ◽  
Atsushi Sato ◽  
Michio Takeyama ◽  
Shun-ichiro Iemura ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Neural Development ◽  
Marker Genes ◽  
Neural Structure ◽  
Animal Pole ◽  
Endogenous Expression ◽  
Myocyte Enhancer Factor ◽  
Molecular Events ◽  
Bone Morphogenic Protein 4 ◽  
Enhancer Factor

ABSTRACT The development of anterior neural structure in Xenopus laevis requires the inhibition of bone morphogenic protein 4 and Wnt signaling. We previously reported that Nemo-like kinase (NLK) negatively regulates Wnt signaling via the phosphorylation of T-cell factor/lymphoid enhancer factor. However, the molecular events occurring downstream of NLK pathways in early neural development remain unclear. In the present study, we identified the transcription factor myocyte enhancer factor 2A (MEF2A) as a novel substrate for NLK. NLK regulates the function of Xenopus MEF2A (xMEF2A) via phosphorylation, and this modification can be inhibited by the depletion of endogenous NLK. In Xenopus embryos, the depletion of either NLK or MEF2A results in a severe defect in anterior development. The endogenous expression of anterior markers was blocked by the depletion of endogenous Xenopus NLK (xNLK) or xMEF2A but, notably, not by the depletion of other xMEF2 family proteins, xMEF2C and xMEF2D. Defects in head formation or the expression of the anterior marker genes caused by the depletion of endogenous xMEF2A could be eliminated by the expression of wild-type xMEF2A, but not xMEF2A containing mutated xNLK phosphorylation sites. Furthermore, the expression of xNLK-induced anterior markers was efficiently blocked by the depletion of endogenous xMEF2A in animal pole explants. These results show that NLK specifically regulates the MEF2A activity required for anterior formation in Xenopus development.

XBF-2 is a transcriptional repressor that converts ectoderm into neural tissue

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5019-5031 ◽  
Author(s):  
F.V. Mariani ◽  
R.M. Harland
Keyword(s):  
Dna Binding ◽  
Neural Development ◽  
Ectopic Expression ◽  
Transcriptional Repressor ◽  
Neural Plate ◽  
Binding Domain ◽  
Expression Cloning ◽  
Dna Binding Domain ◽  
Neural Fate ◽  
Striking Contrast

We have identified Xenopus Brain Factor 2 (XBF-2) as a potent neuralizing activity in an expression cloning screen. In ectodermal explants, XBF-2 converts cells from an epidermal to a neural fate. Such explants contain neurons with distinct axonal profiles and express both anterior and posterior central nervous system (CNS) markers. In striking contrast to X-ngnR-1a or X-NeuroD, ectopic expression of XBF-2 in Xenopus embryos results in an expansion of the neural plate to the ventral midline. The enlarged neural plate consists predominantly of undifferentiated neurons. XBF-2 lies downstream of the BMP antagonists noggin, cerberus, and gremlin since ectodermal explants expressing these molecules exhibit strong expression of XBF-2. While XBF-2 does not upregulate the expression of secreted neural inducers, it downregulates the transcription of BMP-4, an epidermal inducer. We show that XBF-2 acts as a transcriptional repressor and that its effects can be phenocopied with either the engrailed or hairy repressor domain fused to the XBF-2 DNA-binding domain. A fusion of the DNA-binding domain to the activator domain of VP16 blocks the effects of XBF-2 and prevents neural plate development in the embryo. This provides evidence that a transcriptional repressor can affect both regional neural development and neurogenesis in vertebrates.

scholarly journals Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

2002 ◽  
Vol 2 ◽  
pp. 1147-1166 ◽  
Author(s):  
Sally A. Moody ◽  
Hyun-Soo Je
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Stem Cells ◽  
Neural Development ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Neural Induction ◽  
Neural Plate ◽  
Natural Rate ◽  
Neural Fate

The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

scholarly journals Wnt Signaling in Vertebrate Neural Development and Function

2012 ◽  
Vol 7 (4) ◽  
pp. 774-787 ◽  
Author(s):  
Kimberly A. Mulligan ◽  
Benjamin N. R. Cheyette
Keyword(s):  
Wnt Signaling ◽  
Neural Development ◽  
And Function
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