Overexpression of Egr1 Transcription Regulator Contributes to
Schwann Cell Differentiation Defects in Neural Crest-Specific
Adar1 Knockout Mice

J 2024

Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice

ZERAD, Lisa; Nadjet GACEM; Fanny GAYDA; Lucie DAY; Ketty SINIGAGLIA et al.

Základní údaje

Originální název

Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice

Autoři

Vydání

Advances in Fuel Cells, BASEL, Elsevier, 2024, 2073-4409

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.200

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/24:00139746

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

Schwann cells; differentiation; ADAR1; MAVS; EGR1; neural crest

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 6. 2025 15:51, Mgr. Eva Dubská

Anotace

V originále

Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of Adar1 reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of Adar1 mutant phenotypes. By analyzing RNA-Seq data from the sciatic nerves of mouse pups after conditional neural crest deletion of Adar1 (Adar1cKO), we here identified the transcription factors deregulated in Adar1cKO mutants compared to the controls. Through Adar1;Mavs and Adar1cKO;Egr1 double-mutant mouse rescue analyses, we then highlighted that the aberrant activation of the Mavs adapter protein and overexpression of the early growth response 1 (EGR1) transcription factor contribute to the Adar1 deletion associated defects in Schwann cell development in vivo. In silico and in vitro gene regulation studies additionally suggested that EGR1 might mediate this inhibitory effect through the aberrant regulation of EGR2-regulated myelin genes. We thus demonstrate the role of the Mda5/Mavs pathway, but also that of the Schwann cell transcription factors in Adar1-associated peripheral myelination defects.

Návaznosti

GA19-16963S, projekt VaV

Název: Genetický model myši pro studium kontroly interferonu a zánětu

Investor: Grantová agentura ČR, A mouse genetic model to study the control of interferon and inflammation

GX21-27329X, projekt VaV

Název: ADAR-dependentní RNA editace; Jak imunitní systém a mozek porušují Centrální Dogma.

Investor: Grantová agentura ČR, ADAR RNA editing, how immune systems and brains breach The Central Dogma

Citovat

ZERAD, Lisa; Nadjet GACEM; Fanny GAYDA; Lucie DAY; Ketty SINIGAGLIA; Laurence RICHARD; Melanie PARISOT; Nicolas CAGNARD; Stephane MATHIS; Christine BOLE-FEYSOT; Mary Anne O'CONNELL; Veronique PINGAULT; Emilie DAMBROISE; Liam KEEGAN; Jean Michel VALLAT a Nadege BONDURAND. Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice. Advances in Fuel Cells. BASEL: Elsevier, 2024, roč. 13, č. 23, s. 1-23. ISSN 2073-4409. Dostupné z: https://doi.org/10.3390/cells13231952.

@article{2482621,
   author = {Zerad, Lisa and Gacem, Nadjet and Gayda, Fanny and Day, Lucie and Sinigaglia, Ketty and Richard, Laurence and Parisot, Melanie and Cagnard, Nicolas and Mathis, Stephane and BoleandFeysot, Christine and O'Connell, Mary Anne and Pingault, Veronique and Dambroise, Emilie and Keegan, Liam and Vallat, Jean Michel and Bondurand, Nadege},
   article_location = {BASEL},
   article_number = {23},
   doi = {https://doi.org/10.3390/cells13231952},
   keywords = {Schwann cells; differentiation; ADAR1; MAVS; EGR1; neural crest},
   language = {eng},
   issn = {2073-4409},
   journal = {Advances in Fuel Cells},
   title = {Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice},
   url = {https://www.mdpi.com/2073-4409/13/23/1952},
   volume = {13},
   year = {2024}
}

TY  - JOUR
ID  - 2482621
AU  - Zerad, Lisa - Gacem, Nadjet - Gayda, Fanny - Day, Lucie - Sinigaglia, Ketty - Richard, Laurence - Parisot, Melanie - Cagnard, Nicolas - Mathis, Stephane - Bole-Feysot, Christine - O'Connell, Mary Anne - Pingault, Veronique - Dambroise, Emilie - Keegan, Liam - Vallat, Jean Michel - Bondurand, Nadege
PY  - 2024
TI  - Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice
JF  - Advances in Fuel Cells
VL  - 13
IS  - 23
SP  - 1-23
EP  - 1-23
PB  - Elsevier
SN  - 20734409
KW  - Schwann cells
KW  - differentiation
KW  - ADAR1
KW  - MAVS
KW  - EGR1
KW  - neural crest
UR  - https://www.mdpi.com/2073-4409/13/23/1952
N2  - Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of Adar1 reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of Adar1 mutant phenotypes. By analyzing RNA-Seq data from the sciatic nerves of mouse pups after conditional neural crest deletion of Adar1 (Adar1cKO), we here identified the transcription factors deregulated in Adar1cKO mutants compared to the controls. Through Adar1;Mavs and Adar1cKO;Egr1 double-mutant mouse rescue analyses, we then highlighted that the aberrant activation of the Mavs adapter protein and overexpression of the early growth response 1 (EGR1) transcription factor contribute to the Adar1 deletion associated defects in Schwann cell development in vivo. In silico and in vitro gene regulation studies additionally suggested that EGR1 might mediate this inhibitory effect through the aberrant regulation of EGR2-regulated myelin genes. We thus demonstrate the role of the Mda5/Mavs pathway, but also that of the Schwann cell transcription factors in Adar1-associated peripheral myelination defects.
ER  -

ZERAD, Lisa; Nadjet GACEM; Fanny GAYDA; Lucie DAY; Ketty SINIGAGLIA; Laurence RICHARD; Melanie PARISOT; Nicolas CAGNARD; Stephane MATHIS; Christine BOLE-FEYSOT; Mary Anne O'CONNELL; Veronique PINGAULT; Emilie DAMBROISE; Liam KEEGAN; Jean Michel VALLAT a Nadege BONDURAND. Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Adar1 Knockout Mice. \textit{Advances in Fuel Cells}. BASEL: Elsevier, 2024, roč.~13, č.~23, s.~1-23. ISSN~2073-4409. Dostupné z: https://doi.org/10.3390/cells13231952.

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