Signal transduction describes the cellular response to the environment through molecular interactions that elicit functional attributes. Cell surface receptors perceive extracellular signals initiating a cascade of activities that ultimately activate transcription factors that regulate target gene expression. When signaling in one pathway stimulates target gene expression in a second, biochemically distinct pathway, this phenomenon is referred to as ‘intracellular crosstalk’. Cell signaling and intracellular crosstalk are essential and complex physiological processes important for healthy biological development, normal organ homeostasis, pathogen stress responses, and tissue injury repair. Aberrant regulation of signaling pathways alters cell behavior and subverts their normal functions leading to serious diseases in humans, such as hypertension, heart disease, diabetes, cancer, neurodegeneration, inflammation, fibrosis, and many forms of mental illness. However, elucidating the role of a signaling pathway or crosstalk pair in a particular disease pathology is often challenging, as success depends on the experimental context and model organism.

Since the complete annotation of the zebrafish genome, revealing more than 26,000 protein-coding genes with ~70% orthology to disease-causing human genes, these aquatic fish have become great contributors to many biological discoveries. Consistently, genetic studies in humans and zebrafish have revealed that similarities at the morphological and cellular level reflect homologies at the molecular level. Indeed, our current knowledge of vertebrate biology and embryogenesis has been significantly extended using these economically feasible, genetically tractable, and easily accessible organisms that enable in vivo and real-time studies. Importantly, zebrafish have also emerged as powerful disease models that recapitulate the detailed characteristics, etiologies, and progressions of clinically relevant human pathophysiological, neurobehavioral, and psychological impairments, to name a few. Undeniably, the multitude of molecular pathways in these animals that parallel those driving human disease suggests that these fish still hold further promise to continuously enhance our understanding of the detailed roles of specific genes in human diseases, both rare and common. Thus, it is imperative that we continue to highlight the multitude of achievements using these fish models to fully appreciate the advantages of the zebrafish and provide a useful resource to researchers considering the alternative use of these animals in studies of human disorders.

The aim of this Research Topic is to present studies utilizing zebrafish models to understand aspects of cell functionality and discover novel genes and molecular mechanisms in major cell-cell signaling pathways implicated in human disease pathology. We encourage submissions of all article types falling under:

• Autoimmunity/inflammation
• Oncology
• Metabolic disease
• Neurodegeneration
• Cardiac and skeletal muscle diseases

More information on article types accepted by the journal can be found here.

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Frontiers in Cell and Developmental Biology

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