The ribosome biogenesis protein Esf1 is essential for pharyngeal cartilage formation in zebrafish

Chen, Jian Yang; Tan, Xungang; Wang, Zheng Hua; Liu, Yun Zhang; Zhou, Jian Feng; Rong, Xiao Zhi; Lü, Ling; Li, Yun

doi:10.1111/febs.14622

Cited by 25 publications

(17 citation statements)

References 61 publications

(76 reference statements)

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“…Our discovery that PAX9 also has a role in ribosome biogenesis supports a link between these craniofacial phenotypes and ribosome biogenesis, as has been observed for other ribosomopathies [29,67,68]. In different models, ribosomopathies appear to have a predilection for the neural crest, a key component in facial development [14,29,[69][70][71][72][73][74][75]. The neural crest is a population…”

Section: Pax9 Depletion In X Tropicalis Disrupts Craniofacial Develosupporting

confidence: 73%

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

et al. 2020

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Dysregulation of ribosome production can lead to a number of developmental disorders called ribosomopathies. Despite the ubiquitous requirement for these cellular machines used in protein synthesis, ribosomopathies manifest in a tissue-specific manner, with many affecting the development of the face. Here we reveal yet another connection between craniofacial development and making ribosomes through the protein Paired Box 9 (PAX9). PAX9 functions as an RNA Polymerase II transcription factor to regulate the expression of proteins required for craniofacial and tooth development in humans. We now expand this function of PAX9 by demonstrating that PAX9 acts outside of the cell nucleolus to regulate the levels of proteins critical for building the small subunit of the ribosome. This function of PAX9 is conserved to the organism Xenopus tropicalis, an established model for human ribosomopathies. Depletion of pax9 leads to craniofacial defects due to abnormalities in neural crest development, a result consistent with that found for depletion of other ribosome biogenesis factors. This work highlights an unexpected layer of how the making of ribosomes is regulated in human cells and during embryonic development.

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Section: Pax9 Depletion In X Tropicalis Disrupts Craniofacial Develosupporting

confidence: 73%

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

et al. 2020

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“…Ribosome assembly defects might leave neural crest cells unable to produce essential new proteins required for their developmental programme or migration (Calo et al, 2018). For example, zebrafish with mutations in 18S rRNA factor 1 (esf1) have severe pharyngeal cartilage loss due to deficits in cranial neural crest cell development (Chen et al, 2018). Esf1 mutants also show increased apoptosis and p53 signalling.…”

Section: Discussionmentioning

confidence: 99%

RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levels

et al. 2020

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The RNA exosome is a ubiquitously expressed complex of nine core proteins (EXOSC1-9) and associated nucleases responsible for RNA processing and degradation. Mutations in EXOSC3, EXOSC8, EXOSC9, and the exosome cofactor RBM7 cause pontocerebellar hypoplasia and motor neuronopathy. We investigated the consequences of exosome mutations on RNA metabolism and cellular survival in zebrafish and human cell models. We observed that levels of mRNAs encoding p53 and ribosome biogenesis factors are increased in zebrafish lines with homozygous mutations of exosc8 or exosc9, respectively. Consistent with higher p53 levels, mutant zebrafish have a reduced head size, smaller brain, and cerebellum caused by an increased number of apoptotic cells during development. Down-regulation of EXOSC8 and EXOSC9 in human cells leads to p53 protein stabilisation and G2/M cell cycle arrest. Increased p53 transcript levels were also observed in muscle samples from patients with EXOSC9 mutations. Our work provides explanation for the pathogenesis of exosome-related disorders and highlights the link between exosome function, ribosome biogenesis, and p53-dependent signalling. We suggest that exosome-related disorders could be classified as ribosomopathies.

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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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The ribosome biogenesis protein Esf1 is essential for pharyngeal cartilage formation in zebrafish

Cited by 25 publications

References 61 publications

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levels

Vitamin E is necessary for zebrafish nervous system development

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