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Xenopus Models of Organogenesis and Disease

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.00143

Dynamin binding protein is required for Xenopus laevis kidney development

  • 1McGovern Medical School, University of Texas, United States
  • 2Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas, United States
  • 3Department of Pediatrics, Pediatric Research Center, University of Texas Health Science Center at Houston, United States
  • 4Graduate School of Biomedical Sciences, MD Anderson Cancer Center, United States
  • 5Program in Genetics and Epigenetics, University of Texas MD Anderson Cancer Center, University of Texas Health Science Center Graduate School of Biomedical Sciences, United States
  • 6Department of Genetics, University of Texas MD Anderson Cancer Center, United States

The adult human kidney contains over one million nephrons, with each nephron consisting of a tube containing segments that have specialized functions in nutrient and water absorption and waste excretion. The embryonic kidney of Xenopus laevis consists of a single functional nephron composed of regions that are analogous to those found in the human nephron, making it a simple model for the study of nephrogenesis. The exocyst complex, which traffics proteins to the cell membrane in vesicles via CDC42, is essential for normal kidney development. Here, we show that the CDC42-GEF, dynamin binding protein (Dnmbp/Tuba), is essential for nephrogenesis in Xenopus. dnmbp is expressed in Xenopus embryo kidneys during development, and knockdown of Dnmbp using two separate morpholino antisense oligonucleotides results in reduced expression of late pronephric markers, whereas the expression of early markers of nephrogenesis remains unchanged. A greater reduction in expression of markers of differentiated distal and connecting tubules was seen in comparison to proximal tubule markers, indicating that Dnmbp reduction may have a greater impact on distal and connecting tubule differentiation. Additionally, Dnmbp reduction results in glomus and ciliary defects. dnmbp knockout using CRISPR results in a similar reduction of late markers of pronephric tubulogenesis and also results in edema formation in later stage embryos. Overexpression of dnmbp in the kidney also resulted in disrupted pronephric tubules, suggesting that dnmbp levels in the developing kidney are tightly regulated, with either increased or decreased levels leading to developmental defects. Together, these data suggest that Dnmbp is required for nephrogenesis.

Keywords: CRISPR, Pronephros, Nephrogenesis, Xenopus, Tuba, DNMBP

Received: 14 Sep 2018; Accepted: 07 Feb 2019.

Edited by:

Karen Liu, King's College London, United Kingdom

Reviewed by:

Oliver Wessely, Cleveland Clinic, Lerner Research Institute, United States
Mustafa Khokha, School of Medicine, Yale University, United States  

Copyright: © 2019 DeLay, Baldwin and Miller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rachel K. Miller, University of Texas Health Science Center at Houston, Department of Pediatrics, Pediatric Research Center, Houston, 77030, Texas, United States, rachel.k.miller@uth.tmc.edu