Mitochondrial dysfunction interferes with neural crest specification through the FoxD3 transcription factor

Costa, Roberto; Muccioli, Silvia; Brillo, Valentina; Bachmann, Magdalena; Szabó, Ildikò; Leanza, Luigi

doi:10.1016/j.phrs.2020.105385

Cited by 8 publications

(6 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the epithelial-to-mesenchymal transition (EMT), NCCs increase both ribosome biosynthesis 45 and aerobic glycolysis 46 . While glycolytic genes were upregulated in our 45,X NCC transcriptomes, down-regulated transcripts included genes in oxidative phosphorylation, which has also been linked to NCC specification 47 (Fig. 3, Table S1).…”

Section: Discussionmentioning

confidence: 85%

“…During the epithelial-to-mesenchymal transition (EMT), NCCs increase both ribosome biosynthesis 40 and aerobic glycolysis 41 , but our 45,X NCC transcriptomes suggest these processes are decoupled, as many ribosomal proteins are down-while glycolytic genes are up-regulated (Fig. 3, Table S1), at the expense of oxidative phosphorylation, which has also been linked to NCC specification 42 . In addition, cholesterol biosynthesis genes are significantly upregulated in 45,X NCCs, which while critical for modulating NCC signaling 43 may also alter their patterning 44 , and is independently consistent with hypercholesteremia seen in TS patients 5,24 .…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network

Ahern

Bansal

Faustino

et al. 2023

Preprint

View full text Add to dashboard Cite

SUMMARYModeling the developmental etiology of viable human aneuploidies can be challenging in rodent models, where synteny with human chromosomes is affected, or primate-specific biology is implicated. In humans, monosomy-X (45,X) causes Turner syndrome (TS), altering craniofacial, skeletal, endocrine, and cardiovascular development, which remain largely unaffected in 39,X-mice. We derived human 45,X and isogenic euploid induced pluripotent stem cells (hiPSCs) from male and female mosaics to model how human monosomy-X may impact early embryonic development. Because several neural crest (NC) derived cell types are hypothesized to underpin craniofacial and cardiovascular changes in TS, we derived anterior neural crest from our hiPSCs and performed a highly-powered and extensive differential expression study. Across all three isogenic panels, 45,X neural crest cells (NCCs) show impaired acquisition of the PAX7/SOX10 double-positive NC state relative to euploid 46,XY controls. Monosomy-X NCCs also share similarly disrupted expression of NC-specific genes relative to their isogenic euploid control regardless of whether the latter carry an inactive X or Y. Gene-set enrichment analyses indicate monosomy-X NCCs increase cholesterol biosynthesis genes while dampening ribosomal protein and nuclear-encoded mitochondrial genes. These metabolic pathways are also over-represented in gene modules that are preserved in monogenic conditions involving neurocristopathy. Importantly, these gene modules are also significantly enriched in 28% of all TS-associated terms of the human phenotype ontology, and point to specific sex-linked genes that are expressed from two copies in euploid males and females alike, which may qualify as candidate haploinsufficient drivers of TS phenotypes in NC-derived lineages. Our study demonstrates that isogenic hiPSC-derived NCC panels representing monosomy-X can serve as a powerful model of early NC development in TS, and provides euploid and X-monosomic transcriptomic datasets relevant to exploration of TS and NC biology.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 92%

Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network

Ahern

Bansal

Faustino

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, recent evidence has demonstrated an interplay between mitochondrial fitness (energy production and dynamics) and the Wnt pathway. A decrease in mitochondrial ATP synthesis induces ER stress which, in turn, impairs β-catenin stability, ultimately reducing the expression of Wnt-related genes [ 126 ], as it was demonstrated in a mitochondrial disease model of GRACILE syndrome due to impaired complex III function [ 127 ].…”

Section: Mitochondria In Nscs Fate Decisionmentioning

confidence: 99%

Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases

Garone,

De Giorgio,

Carli

2024

J Transl Med

View full text Add to dashboard Cite

Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during neural development and maintenance.During embryonic and adult neurogenesis, NSCs undergo a metabolic switch from glycolytic to oxidative phosphorylation with a rise in mitochondrial DNA (mtDNA) content, changes in mitochondria shape and size, and a physiological augmentation of mitochondrial reactive oxygen species which together drive NSCs to proliferate and differentiate. Genetic and epigenetic modifications of proteins involved in cellular differentiation (Mechanistic Target of Rapamycin), proliferation (Wingless-type), and hypoxia (Mitogen-activated protein kinase)–and all connected by the common key regulatory factor Hypoxia Inducible Factor-1A–are deemed to be responsible for the metabolic shift and, consequently, NSC fate in physiological and pathological conditions.Both primary mitochondrial dysfunction due to mutations in nuclear DNA or mtDNA or secondary mitochondrial dysfunction in oxidative phosphorylation (OXPHOS) metabolism, mitochondrial dynamics, and organelle interplay pathways can contribute to the development of neurodevelopmental or progressive neurodegenerative disorders.This review analyses the physiology and pathology of neural development starting from the available in vitro and in vivo models and highlights the current knowledge concerning key mitochondrial pathways involved in this process.

show abstract

“…The winged-helix transcription factor FoxD3 functions to maintain stemness in chick and is differentially regulated in distinct NCC subpopulations ( Simoes-Costa et al, 2012 ). The expression of FoxD3 is controlled by multiple factors including the Wnt signaling pathway in zebrafish and chick ( Costa et al, 2021 ; Simoes-Costa et al, 2015 ), Pax3 and Zic1 in X. laevis ( Plouhinec et al, 2014 ) and Cdx4 in the zebrafish trunk ( Rocha et al, 2021 ). FoxD3 regulates tetraspanin 18 ( Tspan18 ) expression in the chick cranial NCC ( Fairchild and Gammill, 2013 ).…”

Section: Classical Factors In Ncc Formation and Emtmentioning

confidence: 99%

Time to go: neural crest cell epithelial-to-mesenchymal transition

Leathers

Rogers

2022

Development

View full text Add to dashboard Cite

Neural crest cells (NCCs) are a dynamic, multipotent, vertebrate-specific population of embryonic stem cells. These ectodermally-derived cells contribute to diverse tissue types in developing embryos including craniofacial bone and cartilage, the peripheral and enteric nervous systems and pigment cells, among a host of other cell types. Due to their contribution to a significant number of adult tissue types, the mechanisms that drive their formation, migration and differentiation are highly studied. NCCs have a unique ability to transition from tightly adherent epithelial cells to mesenchymal and migratory cells by altering their polarity, expression of cell-cell adhesion molecules and gaining invasive abilities. In this Review, we discuss classical and emerging factors driving NCC epithelial-to-mesenchymal transition and migration, highlighting the role of signaling and transcription factors, as well as novel modifying factors including chromatin remodelers, small RNAs and post-translational regulators, which control the availability and longevity of major NCC players.

show abstract

Mitochondrial dysfunction interferes with neural crest specification through the FoxD3 transcription factor

Cited by 8 publications

References 63 publications

Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network

Isogenic hiPSC models of Turner syndrome development reveal shared roles of inactive X and Y in the human cranial neural crest network

Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases

Time to go: neural crest cell epithelial-to-mesenchymal transition

Contact Info

Product

Resources

About