Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development.

Cilia are microtubule-based organelles that project from the cell surface. In humans and other vertebrates, possession of a single cilium structure enables an assortment of cellular processes ranging from mechanosensation to fluid propulsion and locomotion. Interestingly, cells can possess a single cilium or many more, where so-called multiciliated cells (MCCs) possess apical membrane complexes with several dozen or even hundreds of motile cilia that beat in a coordinated fashion.

Identification, conservation, and expression of tiered pharmacogenes in zebrafish.

The number of adverse drug events in the United States is critically high, with annual rates exceeding 1 million cases over the last nine years. One cause of adverse drug events is the underlying genetic variation that can alter drug responses. Pharmacogenomics is a growing field that seeks to better understand the relationship between a patient's genetics and drug efficacy.

Ppargc1a Controls Ciliated Cell Development by Regulating Prostaglandin Biosynthesis.

Cilia are microtubule-based organelles that function in a multitude of physiological contexts to perform chemosensing, mechanosensing, and fluid propulsion. The process of ciliogenesis is highly regulated, and disruptions result in disease states termed ciliopathies. Here, we report that peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (ppargc1a) is essential for ciliogenesis in nodal, mono-, and multiciliated cells (MCCs) and for discernment of renal tubule ciliated cell fate during embryogenesis.

Advances in understanding vertebrate nephrogenesis.

The kidney is a complex organ that performs essential functions such as blood filtration and fluid homeostasis, among others. Recent years have heralded significant advancements in our knowledge of the mechanisms that control kidney formation. Here, we provide an overview of vertebrate renal development with a focus on nephrogenesis, the process of generating the epithelialized functional units of the kidney.

PGC-1α in Disease: Recent Renal Insights into a Versatile Metabolic Regulator.

Peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) is perhaps best known as a master regulator of mitochondrial biogenesis and function. However, by virtue of its interactions as a coactivator for numerous nuclear receptors and transcription factors, PGC-1α also regulates many tissue-specific tasks that include adipogenesis, angiogenesis, gluconeogenesis, heme biosynthesis, thermogenesis, and cellular protection against degeneration. Knowledge about these functions continue to be discovered with ongoing research.

New zebrafish model for monitoring proximal tubule physiology in genetic and acquired renal Fanconi syndromes.

Inherited and acquired disorders that affect proximal tubule endocytosis and lysosomal processing manifest with improper loss of solutes and proteins. The zebrafish pronephros is conserved with humans and is used to model numerous renal conditions, but has few quantitative measures for proximal tubule function. Here, Chen et al.

Visualizing gene expression during zebrafish pronephros development and regeneration.

The vertebrate kidney is comprised of functional units known as nephrons. Defects in nephron development or activity are a common feature of kidney disease. Current medical treatments are unable to ameliorate the dire consequences of nephron deficit or injury.

Iroquois transcription factor irx2a is required for multiciliated and transporter cell fate decisions during zebrafish pronephros development.

The genetic regulation of nephron patterning during kidney organogenesis remains poorly understood. Nephron tubules in zebrafish are composed of segment populations that have unique absorptive and secretory roles, as well as multiciliated cells (MCCs) that govern fluid flow. Here, we report that the transcription factor iroquois 2a (irx2a) is requisite for zebrafish nephrogenesis.

Prostaglandin signaling regulates renal multiciliated cell specification and maturation.

Multiciliated cells (MCCs) are specialized epithelia with apical bundles of motile cilia that direct fluid flow. MCC dysfunction is associated with human diseases of the respiratory, reproductive, and central nervous systems. Further, the appearance of renal MCCs has been cataloged in several kidney conditions, where their function is unknown.

Homeogene emx1 is required for nephron distal segment development in zebrafish.

Vertebrate kidneys contain nephron functional units where specialized epithelial cell types are organized into segments with discrete physiological roles. Many gaps remain in our understanding of how segment regions develop. Here, we report that the transcription factor empty spiracles homeobox gene 1 (emx1) is a novel nephron segment regulator during embryonic kidney development in zebrafish.

controls nephron segmentation during zebrafish embryonic kidney ontogeny.

Nephron segmentation involves a concert of genetic and molecular signals that are not fully understood. Through a chemical screen, we discovered that alteration of peroxisome proliferator-activated receptor (PPAR) signaling disrupts nephron segmentation in the zebrafish embryonic kidney (Poureetezadi et al., 2016).

Prostaglandin signaling regulates nephron segment patterning of renal progenitors during zebrafish kidney development.

Kidney formation involves patterning events that induce renal progenitors to form nephrons with an intricate composition of multiple segments. Here, we performed a chemical genetic screen using zebrafish and discovered that prostaglandins, lipid mediators involved in many physiological functions, influenced pronephros segmentation. Modulating levels of prostaglandin E2 (PGE) or PGB restricted distal segment formation and expanded a proximal segment lineage.

Evolving technology: creating kidney organoids from stem cells.

The kidney is a complex organ whose excretory and regulatory functions are vital for maintaining homeostasis. Previous techniques used to study the kidney, including various animal models and 2D cell culture systems to investigate the mechanisms of renal development and regeneration have many benefits but also possess inherent shortcomings. Some of those limitations can be addressed using the emerging technology of 3D organoids.