Comparative Transcriptomics Between Zebrafish and Mammals: A Roadmap for Discovery of Conserved and Unique Signaling Pathways in Physiology and Disease

Shehwana, Huma; Konu, Özlen

doi:10.3389/fcell.2019.00005

Cited by 18 publications

(11 citation statements)

References 39 publications

(68 reference statements)

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“…For example, neurotoxin-induced zebrafish exhibits movement impairments such as decreased swimming speed and abnormal swimming behavior, which is equally translated to bradykinesia-like symptoms in PD patients ( Hughes et al, 2020 ; Robea et al, 2020 ). In terms of genetic factors, genome sequencing analysis revealed that the zebrafish genome is 70% similar to the human genome ( Howe et al, 2013 ; Shehwana and Konu, 2019 ), with 80% of the genes located at the same chromosome and in the same order, implying conserved synteny between these two species ( Barbazuk et al, 2000 ; Howe et al, 2013 ). The genetics of the zebrafish model are well-characterized, and the transgenic models are well-documented ( Kalueff and Cachat, 2011 ).…”

Section: Zebrafish As An Animal Modelmentioning

confidence: 99%

The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

et al. 2021

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The second most prevalent neurodegenerative disorder in the elderly is Parkinson’s disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (Danio rerio) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.

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Section: Zebrafish As An Animal Modelmentioning

confidence: 99%

The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

et al. 2021

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“…Zebrafish as a model organism is widely used to understand disease mechanisms due to its high sequence/functional similarity with humans as well as the availability of a wide range of zebrafish genetic models (Gomes and Mostowy, 2020, Logan et al, 2018, Mickiewicz et al, 2019, Willis et al, 2016, Shehwana and Konu, 2019. Conservation and functional similarity of ace2 and the RAS pathway in zebrafish (Postlethwait et al, 2021) make a disease-focused investigation of zebrafish ace2 expression essential, yet this has remained unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…However, to our knowledge, there is no study investigating the changes in ace2 expression over zebrafish embryonic and larval developmental stages, between genders, and in the different whole adult tissues as well as across different genotypes, treatments, or pathologies. Accordingly, a meta-analysis of differential D r a f t expression of zebrafish ace2, performed across public datasets, may reveal important functionally enriched networks (Shehwana and Konu, 2019).…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of co-expression networks of zebrafish ace2 reveals enrichment of pathways associated with development and disease

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Arici

et al. 2022

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Human Angiotensin I Converting Enzyme 2 (ACE2) plays essential roles in blood pressure regulation and SARS-CoV-2 entry. ACE2 has a highly conserved, one-to-one ortholog, called ace2, in zebrafish, which is an important model for human diseases. However, zebrafish ace2 expression profile has not yet been studied during early development, between genders, across different genotypes, or in disease. Moreover, a network-based meta-analysis for the extraction of functionally enriched pathways associated with differential ace2 expression is lacking in the literature. Herein, we first identified significant development-, tissue-, genotype- and gender-specific modulations in ace2 expression via meta-analysis of zebrafish Affymetrix transcriptomics datasets (ndatasets=107); and the correlation analysis of ace2 meta-differential expression profile revealed distinct positively and negatively correlated local functionally enriched gene networks. Moreover, we demonstrated that ace2 expression was significantly modulated under different physiological and pathological conditions related to development, tissue, gender, diet, infection, and inflammation using additional RNAseq datasets. Our findings implicate a novel translational role for zebrafish ace2 in organ differentiation and pathologies observed in the intestines and liver.

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“…Zebrafish as a model organism is widely used to understand disease mechanisms due to its high sequence/functional similarity with humans as well as the availability of a wide range of zebrafish genetic models (Gomes and Mostowy, 2020;Logan et al, 2018;Mickiewicz et al, 2019;Shehwana and Konu, 2019;Willis et al, 2016). ACE2, identified as the receptor allowing entry of SARS-CoV-2 to the host cell, has a single ortholog in zebrafish with 65% identity (Chou et al, 2006); and the RAS pathway in zebrafish has been shown to be similarly active as in humans (Postlethwait et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

ace2expression is higher in intestines and liver while being tightly regulated in development and disease in zebrafish

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Tombaz

Arici

et al. 2020

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Human Angiotensin I Converting Enzyme 2 (ACE2) that acts as a receptor for SARS-CoV-2 entry is highly expressed in human type II pneumocytes and enterocytes and similarly in other mammals and zebrafish (Danio rerio). The zebrafish genome has a highly conserved, one-to-one ortholog of ACE2, i.e., ace2, whose expression profile however has not yet been studied during development or in pathologies relevant to COVID-19. Herein, we identified significant development-, tissue- and gender-specific modulations in ace2 expression based on meta-analysis of zebrafish Affymetrix transcriptomics datasets (ndatasets=107, GPL1319 in GEO database). Co-expression network analysis of ace2 revealed distinct positively correlated (carboxypeptidase activity and fibrin clot formation), and negatively correlated (cilia biogenesis/transport and chromatin modifications) STRING network modules. Using additional transcriptomics datasets, we showed zebrafish embryos before 3 days post fertilization (dpf) exhibited low levels of ace2 that increased significantly until 4 dpf implicating a role for ace2 in organogenesis. Re-analysis of RNA-seq datasets from zebrafish adult tissues demonstrated ace2 was expressed highly in intestines, variably in liver, and at lower levels in other organs. In addition, zebrafish females and males showed significant dimorphism in their age-dependent expression of ace2, and between ovary and testis where the latter had higher levels. Moreover, we demonstrated ace2 expression was significantly modulated under different physiological and pathological conditions associated with development, diet, infection, and inflammation. Our findings implicate a novel translational role for zebrafish ace2 in differentiation and pathologies predominantly found in intestines and liver, in which the effects of SARS-CoV-2 could be detrimental.

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Comparative Transcriptomics Between Zebrafish and Mammals: A Roadmap for Discovery of Conserved and Unique Signaling Pathways in Physiology and Disease

Cited by 18 publications

References 39 publications

The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

Functional analysis of co-expression networks of zebrafish ace2 reveals enrichment of pathways associated with development and disease

ace2expression is higher in intestines and liver while being tightly regulated in development and disease in zebrafish

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