Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 579-587 ◽  
Author(s):  
K. Mizuseki ◽  
M. Kishi ◽  
M. Matsui ◽  
S. Nakanishi ◽  
Y. Sasai
Keyword(s):  
Neural Differentiation ◽  
Neural Induction ◽  
Extracellular Signals ◽  
Neural Genes ◽  
Factor Expression ◽  
Two Factors ◽  
Pair Rule Gene ◽  
Simultaneous Activation ◽  
Pair Rule

In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor. Expression of the two genes is first detected widely in the prospective neuroectoderm at the beginning of gastrulation, following the onset of Chordin expression and preceding that of Neurogenin (Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. In contrast, Sox-2 alone is not sufficient to cause neural differentiation, but can work synergistically with FGF signaling to initiate neural induction. Thus, Zic-r1 acts in the pathway bridging the neural inducer with the downstream proneural genes, while Sox-2 makes the ectoderm responsive to extracellular signals, demonstrating that the early phase of neural induction involves simultaneous activation of multiple functions.

scholarly journals Combining PLGA Scaffold and MSCs for Brain Tissue Engineering: A Potential Tool for Treatment of Brain Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ling Zhou ◽  
Jiangyi Tu ◽  
Guangbi Fang ◽  
Li Deng ◽  
Xiaoqing Gao ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Neural Differentiation ◽  
Brain Injuries ◽  
Fluorescent Protein ◽  
Neural Induction ◽  
Nerve Tissue ◽  
Induction Medium ◽  
Nuclear Staining ◽  
Plga Scaffold

Nerve tissue engineering is an important strategy for the treatment of brain injuries. Mesenchymal stem cell (MSC) transplantation has been proven to be able to promote repair and functional recovery of brain damage, and poly (lactic-co-glycolic acid) (PLGA) has also been found to have the capability of bearing cells. In the present study, to observe the ability of PLGA scaffold in supporting the adherent growth of MSCs and neurons in vivo and vitro and to assess the effects of PLGA scaffold on proliferation and neural differentiation of MSCs, this study undertakes the following steps. First, MSCs and neurons were cultured and labeled with green fluorescent protein (GFP) or otherwise identified and the PLGA scaffold was synthesized. Next, MSCs and neurons were inoculated on PLGA scaffolds and their adhesion rates were investigated and the proliferation of MSCs was evaluated by using MTT assay. After MSCs were induced by a neural induction medium, the morphological change and neural differentiation of MSCs were detected using scanning electron microscopy (SEM) and immunocytochemistry, respectively. Finally, cell migration and adhesion in the PLGA scaffold in vivo were examined by immunohistochemistry, nuclear staining, and SEM. The experimental results demonstrated that PLGA did not interfere with the proliferation and neural differentiation of MSCs and that MSCs and neuron could grow and migrate in PLGA scaffold. These data suggest that the MSC-PLGA complex may be used as tissue engineering material for brain injuries.

scholarly journals Fgf/Ets signalling in Xenopus ectoderm initiates neural induction and patterning in an autonomous and paracrine manners

2020 ◽  
Author(s):  
Ikuko Hongo ◽  
Harumasa Okamoto
Keyword(s):  
Neural Development ◽  
Neural Induction ◽  
Dominant Negative ◽  
Neural Patterning ◽  
Paracrine Signalling ◽  
Neural Genes ◽  
Morphogenetic Protein ◽  
Bmp Signalling

ABSTRACTFibroblast growth factor (Fgf) and anti-bone morphogenetic protein (Bmp) signals are derived from the organiser of mesoderm origin and cooperate to promote Xenopus neural development from the gastrula ectoderm. Using antisense oligos to Fgf2 and Fgf8 and dominant-negative Ets transcription factors, we showed that the expression of Fgf2, Fgf8, and Ets in ectoderm cells is essential to initiate neural induction both in vivo and in vitro. Our findings show that neural induction is initiated primarily by autonomous signalling in ectoderm cells, rather than by paracrine signalling from organiser cells. The signalling in ectoderm cells is transduced via the Fgf/Ras/Mapk/Ets pathway, independent of Bmp signal inhibition via the Fgf/Ras/Mapk/Smad1 route, as indicated by earlier studies. Through the same pathway, Fgfs activated position-specific neural genes dose-dependently along the anteroposterior axis in cultured ectoderm cells. The expression of these genes coincides with the establishment of the activated Ets gradient within the gastrula ectoderm. Organiser cells, being located posteriorly to the ectoderm, secrete Fgfs as gastrulation proceeds, which among several candidate molecules initially promote neural patterning of the induced neuroectoderm as morphogens.Summary statementFgf/Ets signalling in ectodermal cells is required to initiate the expression of both anterior and posterior neural genes from the late blastula to gastrula stages, independent of anti-Bmp signalling.

scholarly journals Small Mass but Strong Information: Diagnostic Ions Provide Crucial Clues to Correctly Identify Histone Lysine Modifications

Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 18
Author(s):  
Alaa Hseiky ◽  
Marion Crespo ◽  
Sylvie Kieffer-Jaquinod ◽  
François Fenaille ◽  
Delphine Pflieger
Keyword(s):  
Amino Acid ◽  
Small Mass ◽  
Mass Region ◽  
Amino Acid Sequences ◽  
Lysine Modification ◽  
Lysine Residues ◽  
Two Factors ◽  
Low Mass ◽  
Diagnostic Ions

(1) Background: The proteomic analysis of histones constitutes a delicate task due to the combination of two factors: slight variations in the amino acid sequences of variants and the multiplicity of post-translational modifications (PTMs), particularly those occurring on lysine residues. (2) Methods: To dissect the relationship between both aspects, we carefully evaluated PTM identification on lysine 27 from histone H3 (H3K27) and the artefactual chemical modifications that may lead to erroneous PTM determination. H3K27 is a particularly interesting example because it can bear a range of PTMs and it sits nearby residues 29 and 31 that vary between H3 sequence variants. We discuss how the retention times, neutral losses and immonium/diagnostic ions observed in the MS/MS spectra of peptides bearing modified lysines detectable in the low-mass region might help validate the identification of modified sequences. (3) Results: Diagnostic ions carry key information, thereby avoiding potential mis-identifications due to either isobaric PTM combinations or isobaric amino acid-PTM combinations. This also includes cases where chemical formylation or acetylation of peptide N-termini artefactually occurs during sample processing or simply in the timeframe of LC-MS/MS analysis. Finally, in the very subtle case of positional isomers possibly corresponding to a given mass of lysine modification, the immonium and diagnostic ions may allow the identification of the in vivo structure.

scholarly journals Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain

2021 ◽  
Vol 30 ◽  
pp. 096368972097821
Author(s):  
Andrea Tenorio-Mina ◽  
Daniel Cortés ◽  
Joel Esquivel-Estudillo ◽  
Adolfo López-Ornelas ◽  
Alejandro Cabrera-Wrooman ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Ectopic Expression ◽  
Neural Induction ◽  
Human Keratinocytes ◽  
Differentiation Potential ◽  
Neuronal Proteins ◽  
Green Fluorescent

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.

scholarly journals Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors

1999 ◽  
Vol 19 (6) ◽  
pp. 4028-4038 ◽  
Author(s):  
Shen-Hsi Yang ◽  
Alex Galanis ◽  
Andrew D. Sharrocks
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Map Kinases ◽  
Biological Response ◽  
Extracellular Signals ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Mitogen-activated protein (MAP) kinase-mediated signalling to the nucleus is an important event in the conversion of extracellular signals into a cellular response. However, the existence of multiple MAP kinases which phosphorylate similar phosphoacceptor motifs poses a problem in maintaining substrate specificity and hence the correct biological response. Both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) subfamilies of MAP kinases use a second specificity determinant and require docking to their transcription factor substrates to achieve maximal substrate activation. In this study, we demonstrate that among the different MAP kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38α and p38β2. The efficiency of phosphorylation in vitro and transcriptional activation in vivo of MEF2A and MEF2C by these p38 subtypes requires the presence of a kinase docking domain (D-domain). Furthermore, the D-domain from MEF2A is sufficient to confer p38 responsiveness on different transcription factors, and reciprocal effects are observed upon the introduction of alternative D-domains into MEF2A. These results therefore contribute to our understanding of signalling to MEF2 transcription factors and demonstrate that the requirement for substrate binding by MAP kinases is an important facet of three different subclasses of MAP kinases (ERK, JNK, and p38).

odd Oz: A novel Drosophila pair rule gene

Cell ◽  
1994 ◽  
Vol 77 (4) ◽  
pp. 587-598 ◽  
Author(s):  
Anna Levine ◽  
Ayelet Bashan-Ahrend ◽  
Ofra Budai-Hadrian ◽  
Devorah Gartenberg ◽  
Sophia Menasherow ◽  
...  
Keyword(s):  
Pair Rule Gene ◽  
Pair Rule

Plant Exosomes As Novel Nanoplatforms for MicroRNA Transfer Stimulate Neural Differentiation of Stem Cells In Vitro and In Vivo

Nano Letters ◽  
2021 ◽  
Author(s):  
Xue-Han Xu ◽  
Tie-Jun Yuan ◽  
Haseeb Anwar Dad ◽  
Mu-Yang Shi ◽  
Yi-Yu Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Differentiation

Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain

1999 ◽  
Vol 112 (12) ◽  
pp. 2019-2032 ◽  
Author(s):  
A.D. Minet ◽  
B.P. Rubin ◽  
R.P. Tucker ◽  
S. Baumgartner ◽  
R. Chiquet-Ehrismann
Keyword(s):  
Sequence Motifs ◽  
Heparin Binding ◽  
Terminal Part ◽  
Phylogenetic Conservation ◽  
Neuronal Protein ◽  
Repeat Proteins ◽  
Heparin Binding Domain ◽  
Pair Rule Gene ◽  
Pair Rule

The Drosophila gene ten-m is the first pair-rule gene not encoding a transcription factor, but an extracellular protein. We have characterized a highly conserved chicken homologue that we call teneurin-1. The C-terminal part harbors 26 repetitive sequence motifs termed YD-repeats. The YD-repeats are most similar to the core of the rhs elements of Escherichia coli. Related repeats in toxin A of Clostridium difficile are known to bind specific carbohydrates. We show that recombinantly expressed proteins containing the YD-repeats of teneurin-1 bind to heparin. Furthermore, heparin lyase treatment of extracts of cells expressing recombinant YD-repeat protein releases this protein from high molecular mass aggregates. In situ hybridization and immunostaining reveals teneurin-1 expression in neurons of the developing visual system of chicken and Drosophila. This phylogenetic conservation of neuronal expression from flies to birds implies fundamental roles for teneurin-1 in neurogenesis. This is supported by the neurite outgrowth occurring on substrates made of recombinant YD-repeat proteins, which can be inhibited by heparin. Database searches resulted in the identification of ESTs encoding at least three further members of the teneurin family of proteins. Furthermore, the human teneurin-1 gene could be identified on chromosome Xq24/25, a region implied in an X-linked mental retardation syndrome.

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