Lineage-specific requirements of β-catenin in neural crest development

β-Catenin plays a pivotal role in cadherin-mediated cell adhesion. Moreover, it is a downstream signaling component of Wnt that controls multiple developmental processes such as cell proliferation, apoptosis, and fate decisions. To study the role of β-catenin in neural crest development, we used the Cre/loxP system to ablate β-catenin specifically in neural crest stem cells. Although several neural crest–derived structures develop normally, mutant animals lack melanocytes and dorsal root ganglia (DRG). In vivo and in vitro analyses revealed that mutant neural crest cells emigrate but fail to generate an early wave of sensory neurogenesis that is normally marked by the transcription factor neurogenin (ngn) 2. This indicates a role of β-catenin in premigratory or early migratory neural crest and points to heterogeneity of neural crest cells at the earliest stages of crest development. In addition, migratory neural crest cells lateral to the neural tube do not aggregate to form DRG and are unable to produce a later wave of sensory neurogenesis usually marked by the transcription factor ngn1. We propose that the requirement of β-catenin for the specification of melanocytes and sensory neuronal lineages reflects roles of β-catenin both in Wnt signaling and in mediating cell–cell interactions.

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Cancer-associated HIF-2α impacts trunk neural crest stemness

10.1101/2020.01.22.915199 ◽

2020 ◽

Author(s):

Sofie Mohlin ◽

Camilla U. Persson ◽

Elina Fredlund ◽

Emanuela Monni ◽

Jessica M. Lindvall ◽

...

Keyword(s):

Neural Crest ◽

Normal Development ◽

Hypoxia Inducible Factor ◽

Neural Crest Cells ◽

Sympathetic Ganglia ◽

Stem Cell Population ◽

Neural Crest Development ◽

Trunk Neural Crest

AbstractThe neural crest is a stem cell population that gives rise to sympathetic ganglia, the cell type of origin of neuroblastoma. Hypoxia Inducible Factor (HIF)-2α is associated with high risk neuroblastoma, however, little is known about its role in normal neural crest development. To address this important question, here we show that HIF-2α is expressed in trunk neural crest cells of human, murine and avian embryos. Modulating HIF-2α in vivo not only causes developmental delays but also induces proliferation and stemness of neural crest cells while altering the number of cells migrating ventrally to sympathoadrenal sites. Transcriptome changes after loss of HIF-2α reflect the in vivo phenotype. The results suggest that expression levels of HIF-2α must be strictly controlled and abnormal levels increase stemness and may promote metastasis. Our findings help elucidate the role of HIF-2α during normal development with implications also in tumor initiation at the onset of neuroblastoma.

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Progression and Differentiation of Alveolar Rhabdomyosarcoma Is Regulated by PAX7 Transcription Factor—Significance of Tumor Subclones

Cells ◽

10.3390/cells10081870 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1870

Author(s):

Klaudia Skrzypek ◽

Grażyna Adamek ◽

Marta Kot ◽

Bogna Badyra ◽

Marcin Majka

Keyword(s):

Transcription Factor ◽

Cell Lines ◽

Migration Activity ◽

Id Proteins ◽

Rh30 Cell ◽

Str Profile ◽

And Migration

Rhabdomyosarcoma (RMS), is the most frequent soft tissue tumor in children that originates from disturbances in differentiation process. Mechanisms leading to the development of RMS are still poorly understood. Therefore, by analysis of two RMS RH30 cell line subclones, one subclone PAX7 negative, while the second one PAX7 positive, and comparison with other RMS cell lines we aimed at identifying new mechanisms crucial for RMS progression. RH30 subclones were characterized by the same STR profile, but different morphology, rate of proliferation, migration activity and chemotactic abilities in vitro, as well as differences in tumor morphology and growth in vivo. Our analysis indicated a different level of expression of adhesion molecules (e.g., from VLA and ICAM families), myogenic microRNAs, such as miR-206 and transcription factors, such as MYOD, MYOG, SIX1, and ID. Silencing of PAX7 transcription factor with siRNA confirmed the crucial role of PAX7 transcription factor in proliferation, differentiation and migration of RMS cells. To conclude, our results suggest that tumor cell lines with the same STR profile can produce subclones that differ in many features and indicate crucial roles of PAX7 and ID proteins in the development of RMS.

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The use of siRNA as a pharmacological tool to assess a role for the transcription factor NF-IL6 in the brain under in vitro and in vivo conditions during LPS-induced inflammatory stimulation

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0017 ◽

2017 ◽

Vol 28 (6) ◽

Cited By ~ 2

Author(s):

Jelena Damm ◽

Joachim Roth ◽

Rüdiger Gerstberger ◽

Christoph Rummel

Keyword(s):

Transcription Factor ◽

Brain Cells ◽

Nuclear Factor ◽

Si Rna ◽

The Brain ◽

Deficient Mice ◽

Transcription Factor Nuclear Factor

AbstractBackground:Studies with NF-IL6-deficient mice indicate that this transcription factor plays a dual role during systemic inflammation with pro- and anti-inflammatory capacities. Here, we aimed to characterize the role of NF-IL6 specifically within the brain.Methods:In this study, we tested the capacity of short interfering (si) RNA to silence the inflammatory transcription factor nuclear factor-interleukin 6 (NF-IL6) in brain cells underResults:In cells of a mixed neuronal and glial primary culture from the ratConclusions:This approach was, thus, not suitable to characterize the role NF-IL6 in the brain

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In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells

Experimental Neurology ◽

10.1016/j.expneurol.2005.12.015 ◽

2006 ◽

Vol 198 (2) ◽

pp. 438-449 ◽

Cited By ~ 72

Author(s):

Jorge B. Aquino ◽

Jens Hjerling-Leffler ◽

Martin Koltzenburg ◽

Thomas Edlund ◽

Marcelo J. Villar ◽

...

Keyword(s):

Stem Cells ◽

Neural Crest ◽

Schwann Cells ◽

Neural Crest Stem Cells ◽

In Vivo Differentiation

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The Role of the Ets Domain Transcription Factor Erm in Modulating Differentiation of Neural Crest Stem Cells

Developmental Biology ◽

10.1006/dbio.2002.0795 ◽

2002 ◽

Vol 250 (1) ◽

pp. 168-180 ◽

Cited By ~ 28

Author(s):

Christian Paratore ◽

Guya Brugnoli ◽

Hye-Youn Lee ◽

Ueli Suter ◽

Lukas Sommer

Keyword(s):

Stem Cells ◽

Transcription Factor ◽

Neural Crest ◽

Neural Crest Stem Cells ◽

Ets Domain

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The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos

Development ◽

10.1242/dev.128.8.1467 ◽

2001 ◽

Vol 128 (8) ◽

pp. 1467-1479 ◽

Cited By ~ 7

Author(s):

R. Kos ◽

M.V. Reedy ◽

R.L. Johnson ◽

C.A. Erickson

Keyword(s):

Transcription Factors ◽

Neural Crest ◽

Antisense Oligonucleotides ◽

Neural Crest Cells ◽

Winged Helix ◽

Dorsal Neural Tube ◽

Neural Crest Development ◽

Mesenchymal Transformation ◽

Winged Helix Transcription Factor

The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells. Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop. We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.

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Interleukin 1 induces renal CD44 expression in vivo and in vitro: role of the transcription factor Egr-1

Nephrology ◽

10.1046/j.1440-1797.2002.00046.x ◽

2002 ◽

Vol 7 (3) ◽

pp. 136-144

Author(s):

Kazunori Takazoe ◽

Rita Foti ◽

Lynette A Hurst ◽

Hui Y Lan ◽

Robert C Atkins ◽

...

Keyword(s):

Transcription Factor ◽

Interleukin 1 ◽

Cd44 Expression

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Transcription factor Krüppel-like factor 2 plays a vital role in endothelial colony forming cells differentiation

Cardiovascular Research ◽

10.1093/cvr/cvt113 ◽

2013 ◽

Vol 99 (3) ◽

pp. 514-524 ◽

Cited By ~ 20

Author(s):

Yimeng Song ◽

Xiaoxia Li ◽

Dawei Wang ◽

Chenglai Fu ◽

Zhenjiu Zhu ◽

...

Keyword(s):

Transcription Factor ◽

Tube Formation ◽

Vital Role ◽

Ampk Activation ◽

Cell Markers ◽

Endothelial Colony Forming Cells ◽

Angiogenesis Assay

Abstract Aims Endothelial colony forming cells (ECFCs) participate in post-natal vasculogenesis. We previously reported that vascular endothelial growth factor (VEGF) promotes human ECFC differentiation through AMP-activated protein kinase (AMPK) activation. However, the mechanisms underlying transcriptional regulation of ECFC differentiation still remain largely elusive. Here, we investigated the role of transcription factor Krüppel-like factor 2 (KLF2) in the regulation of ECFC function. Methods and results Human ECFCs were isolated from cord blood and cultured. Treatment with VEGF significantly increased endothelial markers in ECFCs and their capacity for migration and tube formation. The mRNA and protein levels of KLF2 were also significantly up-regulated. This up-regulation was abrogated by AMPK inhibition or by knockdown of KLF2 with siRNA. Furthermore, adenovirus-mediated overexpression of KLF2 promoted ECFC differentiation by enhancing expression of endothelial cell markers, reducing expression of progenitor cell markers, and increasing the capacity for tube formation in vitro, indicating the important role of KLF2 in ECFC-mediated angiogenesis. Histone deacetylase 5 (HDAC5) was phosphorylated by AMPK activity induced by VEGF and the AMPK agonist AICAR (5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide). In vivo angiogenesis assay revealed that overexpression of KLF2 in bone-marrow-derived pro-angiogenic progenitor cells promoted vessel formation when the cells were implanted in C57BL/6 mice. Conclusion Up-regulation of KLF2 by AMPK activation constitutes a novel mechanism of ECFC differentiation, and may have therapeutic value in the treatment of ischaemic heart disease.

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