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Journal of Developmental Biology Mar 2023Nephrons are the functional units which comprise the kidney. Each nephron contains a number of physiologically unique populations of specialized epithelial cells that... (Review)
Review
Nephrons are the functional units which comprise the kidney. Each nephron contains a number of physiologically unique populations of specialized epithelial cells that are organized into discrete domains known as segments. The principles of nephron segment development have been the subject of many studies in recent years. Understanding the mechanisms of nephrogenesis has enormous potential to expand our knowledge about the basis of congenital anomalies of the kidney and urinary tract (CAKUT), and to contribute to ongoing regenerative medicine efforts aimed at identifying renal repair mechanisms and generating replacement kidney tissue. The study of the zebrafish embryonic kidney, or pronephros, provides many opportunities to identify the genes and signaling pathways that control nephron segment development. Here, we describe recent advances of nephron segment patterning and differentiation in the zebrafish, with a focus on distal segment formation.
PubMed: 36976103
DOI: 10.3390/jdb11010014 -
Pediatric Nephrology (Berlin, Germany) Sep 2011Kidney development is a multi-step process where undifferentiated mesenchyme is converted into a highly complex organ through several inductive events. The general... (Review)
Review
Kidney development is a multi-step process where undifferentiated mesenchyme is converted into a highly complex organ through several inductive events. The general principles regulating these events have been under intense investigation and despite extensive progress, many open questions remain. While the metanephric kidneys of mouse and rat have served as the primary model, other organisms also significantly contribute to the field. In particular, the more primitive pronephric kidney has emerged as an alternative model due to its simplicity and experimental accessibility. Many aspects of nephron development such as the patterning along its proximo-distal axis are evolutionarily conserved and are therefore directly applicable to higher vertebrates. This review will focus on the current understanding of pronephros development in Xenopus. It summarizes how signaling, transcriptional regulation, as well as post-transcriptional mechanisms contribute to the differentiation of renal epithelial cells. The data show that even in the simple pronephros the mechanisms regulating kidney organogenesis are highly complex. It also illustrates that a multifaceted analysis embracing modern genome-wide approaches combined with single gene analysis will be required to fully understand all the intricacies.
Topics: Animals; Developmental Biology; Epithelial Cells; Gene Expression Regulation, Developmental; History, 20th Century; History, 21st Century; Organogenesis; Pronephros; Signal Transduction; Xenopus
PubMed: 21499947
DOI: 10.1007/s00467-011-1881-2 -
Nephron. Experimental Nephrology 2006An understanding of the regulation of kidney development has increased dramatically in the past decade. The pronephros, mesonephros, and metanephros represent three... (Review)
Review
An understanding of the regulation of kidney development has increased dramatically in the past decade. The pronephros, mesonephros, and metanephros represent three distinct renal organs that function, in succession, as the vertebrate excretory system during development of the kidney. These three organ systems are derived from the intermediate mesoderm and develop in a well-defined temporal and spatial sequence. The pronephros, which consists of a tubule, duct and glomus, is established first and is the simplest of the excretory organs in vertebrates. Xenopus pronephros serves as an ideal model for investigating organogenesis and development of renal function in vertebrates. In this article, we highlight the advantages of Xenopus for analyzing kidney organogenesis and the latest research in pronephros development.
Topics: Animals; Embryonic Development; Kidney; Xenopus laevis
PubMed: 16554664
DOI: 10.1159/000092192 -
Clinical Science (London, England :... Dec 2018The renin-angiotensin system (RAS) is highly conserved, and components of the RAS are present in all vertebrates to some degree. Although the RAS has been studied since... (Review)
Review
The renin-angiotensin system (RAS) is highly conserved, and components of the RAS are present in all vertebrates to some degree. Although the RAS has been studied since the discovery of renin, its biological role continues to broaden with the identification and characterization of new peptides. The evolutionarily distant zebrafish is a remarkable model for studying the kidney due to its genetic tractability and accessibility for imaging. The zebrafish pronephros is an especially useful kidney model due to its structural simplicity yet complex functionality, including capacity for glomerular and tubular filtration. Both the pronephros and mesonephros contain renin-expressing perivascular cells, which respond to RAS inhibition, making the zebrafish an excellent model for studying the RAS. This review summarizes the physiological and genetic tools currently available for studying the zebrafish kidney with regards to functionality of the RAS, using novel imaging techniques such as SPIM microscopy coupled with targeted single cell ablation and synthesis of vasoactive RAS peptides.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Animals, Genetically Modified; Gene Expression Regulation, Developmental; Kidney Diseases; Luminescent Proteins; Pronephros; Renin-Angiotensin System; Signal Transduction; Zebrafish; Zebrafish Proteins
PubMed: 30518571
DOI: 10.1042/CS20180721 -
Pediatric Nephrology (Berlin, Germany) Apr 2017While kidney donations stagnate, the number of people in need of kidney transplants continues to grow. Although transplanting culture-grown organs is years away,... (Review)
Review
While kidney donations stagnate, the number of people in need of kidney transplants continues to grow. Although transplanting culture-grown organs is years away, pursuing the engineering of the kidney de novo is a valid means of closing the gap between the supply and demand of kidneys for transplantation. The structural organization of a mouse kidney is similar to that of humans. Therefore, mice have traditionally served as the primary model system for the study of kidney development. The mouse is an ideal model organism for understanding the complexity of the human kidney. Nonetheless, the elaborate structure of the mammalian kidney makes the discovery of new therapies based on de novo engineered kidneys more challenging. In contrast to mammals, amphibians have a kidney that is anatomically less complex and develops faster. Given that analogous genetic networks regulate the development of mammalian and amphibian nephric organs, using embryonic kidneys of Xenopus laevis (African clawed frog) to analyze inductive cell signaling events and morphogenesis has many advantages. Pioneering work that led to the ability to generate kidney organoids from embryonic cells was carried out in Xenopus. In this review, we discuss how Xenopus can be utilized to compliment the work performed in mammalian systems to understand kidney development.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Kidney; Models, Biological; Nephrons; Organogenesis; Xenopus
PubMed: 27099217
DOI: 10.1007/s00467-016-3372-y -
Scientific Reports Oct 2023The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary...
The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1). However, few Lhx1-Ldb1 cofactors have been identified for kidney organogenesis. By tandem- affinity purification from kidney-induced Xenopus animal caps, we identified single-stranded DNA binding protein 2 (Ssbp2) interacts with the Ldb1-Lhx1 complex. Ssbp2 is expressed in the Xenopus pronephros, and knockdown prevents normal morphogenesis and differentiation of the glomus and the convoluted renal tubules. We demonstrate a role for a member of the Ssbp family in kidney organogenesis and provide evidence of a fundamental function for the Ldb1-Lhx1-Ssbp transcriptional complexes in embryonic development.
Topics: Animals; Xenopus laevis; LIM-Homeodomain Proteins; Gene Expression Regulation, Developmental; Transcription Factors; Kidney; Embryonic Development; Morphogenesis; Pronephros; Xenopus Proteins; Mammals
PubMed: 37794075
DOI: 10.1038/s41598-023-43662-1 -
BioRxiv : the Preprint Server For... Apr 2023The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary...
The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1). However, few Lhx1-Ldb1 cofactors have been identified for kidney organogenesis. By tandem-affinity purification from kidney-induced animal caps, we identified s ingle- s tranded DNA b inding p rotein 2 (Ssbp2) interacts with the Ldb1-Lhx1 complex. Ssbp2 is expressed in the pronephros, and knockdown prevents normal morphogenesis and differentiation of the glomus and the convoluted renal tubules. We demonstrate a role for a member of the Ssbp family in kidney organogenesis and provide evidence of a fundamental function for the Ldb1-Lhx1-Ssbp transcriptional complexes in embryonic development.
PubMed: 37090653
DOI: 10.1101/2023.04.15.537039 -
Cells Apr 2022The anterior-posterior (AP) axis in chordates is regulated by a conserved set of genes and signaling pathways, including genes and retinoic acid (RA), which play...
The anterior-posterior (AP) axis in chordates is regulated by a conserved set of genes and signaling pathways, including genes and retinoic acid (RA), which play well-characterized roles in the organization of the chordate body plan. The intermediate mesoderm (IM), which gives rise to all vertebrate kidneys, is an example of a tissue that differentiates sequentially along this axis. Yet, the conservation of the spatiotemporal regulation of the IM across vertebrates remains poorly understood. In this study, we used a comparative developmental approach focusing on non-conventional model organisms, a chondrichthyan (catshark), a cyclostome (lamprey), and a cephalochordate (amphioxus), to assess the involvement of RA in the regulation of chordate and vertebrate pronephros formation. We report that the anterior expression boundary of early pronephric markers ( and ), positioned at the level of somite 6 in amniotes, is conserved in the catshark and the lamprey. Furthermore, RA, driving the expression of genes like in amniotes, regulates the anterior pronephros boundary in the catshark. We find no evidence for the involvement of this regulatory hierarchy in the AP positioning of the lamprey pronephros and the amphioxus pronephros homolog, Hatschek's nephridium. This suggests that despite the conservation of and expressions in chordate pronephros homologs, the responsiveness of the IM, and hence of pronephric genes, to RA- and -dependent regulation is a gnathostome novelty.
Topics: Animals; Chordata; Genes, Homeobox; Lampreys; Pronephros; Tretinoin; Vertebrates
PubMed: 35455988
DOI: 10.3390/cells11081304