A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development

Ciarlo, Christie; Kaufman, Charles; Kınıkoğlu, Beste; Michael, Jonathan; Yang, Song; D'Amato, Christopher R.; Blokzijl-Franke, Sasja; Hertog, Jeroen den; Schlaeger, Thorsten M.; Zhou, Yi; Liao, Eric C.; Zon, Leonard I.

doi:10.7554/elife.29145

Cited by 28 publications

(29 citation statements)

References 58 publications

(65 reference statements)

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“…We assessed the overall morphology of akt Δ/Δ embryos at early stages of development. Compared to WT, akt Δ/Δ embryos exhibited a reduction in pigmented cells at 48 hours post fertilization (hpf) ( Figure S1B) consistent with the chemical inhibition of Akt signaling (Ciarlo et al, 2017). Moreover, akt Δ/Δ had normal body and head size ( Figure S1B) and were viable until 6 days post fertilization (dpf), enabling the analysis of specific vascular patterns in during early development.…”

Section: Embryonic Loss Of Akt Results In Artery-vein Malformationsmentioning

confidence: 55%

Akt is required for artery formation during embryonic vascular development

Zhou

Ristori

et al. 2020

Preprint

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One of the first events in the development of the cardiovascular system is morphogenesis of the main embryonic artery, the dorsal aorta (DA). The DA forms via a conserved genetic process mediated by the migration, specification, and organization of endothelial progenitor cells into a distinct arterial lineage and vessel type. Several angiogenic factors activate different signaling pathways to control DA formation, however the physiological relevance of distinct kinases in this complex process remains unclear. Here, we identify the role of Akt during early vascular development by generating mutant zebrafish lines that lack expression of akt isoforms. Live cell imaging coupled with single cell RNA sequencing of akt mutants reveal that Akt is required for proper development of the DA by sustaining arterial cell progenitor specification and segregation. Mechanistically, inhibition of active FOXO in akt mutants rescues impaired arterial development but not the expression of arterial markers, whereas Notch activation rescues arterial marker expression. Our work suggests that Akt activity is critical for early artery development, in part via FOXO and Notch-mediated regulation.

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Section: Embryonic Loss Of Akt Results In Artery-vein Malformationsmentioning

confidence: 55%

Akt is required for artery formation during embryonic vascular development

Zhou

Ristori

et al. 2020

Preprint

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“…NC migration and differentiation is highly dependent on nutrient status 36,37 . Both pax2a and sox10 expression patterns are irregular in oxidative stress models [38][39][40] and errors in neurogenesis are marked by transcriptional changes of the Pax [41][42][43] and SoxE family of genes [43][44][45][46] .…”

mentioning

confidence: 99%

Vitamin E is necessary for zebrafish nervous system development

Head

Tanguay

et al. 2020

Sci Rep

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Vitamin E (VitE) deficiency results in embryonic lethality. Knockdown of the gene ttpa encoding for the VitE regulatory protein [α-tocopherol transfer protein (α-TTP)] in zebrafish embryos causes death within 24 h post-fertilization (hpf). To test the hypothesis that VitE, not just α-TTP, is necessary for nervous system development, adult 5D strain zebrafish, fed either VitE sufficient (E+) or deficient (E−) diets, were spawned to obtain E+ and E− embryos, which were subjected to RNA in situ hybridization and RT-qPCR. Ttpa was expressed ubiquitously in embryos up to 12 hpf. Early gastrulation (6 hpf) assessed by goosecoid expression was unaffected by VitE status. By 24 hpf, embryos expressed ttpa in brain ventricle borders, which showed abnormal closure in E− embryos. They also displayed disrupted patterns of paired box 2a (pax2a) and SRY-box transcription factor 10 (sox10) expression in the midbrain-hindbrain boundary, spinal cord and dorsal root ganglia. In E− embryos, the collagen sheath notochord markers (col2a1a and col9a2) appeared bent. Severe developmental errors in E− embryos were characterized by improper nervous system patterning of the usually carefully programmed transcriptional signals. Histological analysis also showed developmental defects in the formation of the fore-, mid- and hindbrain and somites of E− embryos at 24 hpf. Ttpa expression profile was not altered by the VitE status demonstrating that VitE itself, and not ttpa, is required for development of the brain and peripheral nervous system in this vertebrate embryo model.

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“…In this screen, caffeic acid phenethyl ester (CAPE) was found as an inhibitor of zebrafish neural crest development. Mechanistically, CAPE interrupted sox10-mediated neural crest formation via inhibition of the fibroblast growth factor-stimulated phosphoinositide 3-kinase/Ak strain transforming (PI3K/AKT) signaling axis [95]. This identification of PI3K/AKT as a novel intracellular pathway regulating neural crest differentiation provides further targets for manipulating neural crest identity in melanoma.…”

Section: Zebrafish Neural Crest Reactivation In Melanoma Initiation Amentioning

confidence: 86%

“…More recently, the crestin reporter has been utilized in a chemical genetic screen to identify modulators of neural crest identity [95]. In this screen, caffeic acid phenethyl ester (CAPE) was found as an inhibitor of zebrafish neural crest development.…”

Section: Zebrafish Neural Crest Reactivation In Melanoma Initiation Amentioning

confidence: 99%

From Tank to Treatment: Modeling Melanoma in Zebrafish

Frantz

Ceol

2020

Cells

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Melanoma is the deadliest form of skin cancer and one of few cancers with a growing incidence. A thorough understanding of its pathogenesis is fundamental to developing new strategies to combat mortality and morbidity. Zebrafish—due in large part to their tractable genetics, conserved pathways, and optical properties—have emerged as an excellent system to model melanoma. Zebrafish have been used to study melanoma from a single tumor initiating cell, through metastasis, remission, and finally into relapse. In this review, we examine seminal zebrafish studies that have advanced our understanding of melanoma.

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A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development

Cited by 28 publications

References 58 publications

Akt is required for artery formation during embryonic vascular development

Akt is required for artery formation during embryonic vascular development

Vitamin E is necessary for zebrafish nervous system development

From Tank to Treatment: Modeling Melanoma in Zebrafish

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