title: The transcriptional coactivator Taz regulates proximodistal patterning of the pronephric tubule in zebrafish.
abstract: The zebrafish pronephric tubule consists of proximal and distal segments and a collecting duct. The proximal segment is subdivided into the neck, proximal convoluted tubule (PCT) and proximal straight tubule (PST) segments. The distal segment consists of the distal-early (DE) and distal-late (DL) segments. How the proximal and distal segments develop along the anteroposterior axis is poorly understood. Here we show that knockdown of taz in zebrafish caused shortening and a significant reduction in the number of principal cells of the PST-DE segment, and proximalization of the pronephric tubule in 24 hpf embryos. RA treatment expanded the pronephric proximal domain in normal embryos as in taz morphants, an effect that was further enhanced upon exposure of taz morphants to RA. The early pronephric defects in 24 hpf taz morphants led to the failure of anterior pronephric tubule migration and convolution, and to PCT dilation and cyst formation in older embryos. In situ hybridization showed weak and transient expression of taz at the bud stage in the intermediate mesoderm, the source of pronephric progenitors. The present findings show that Taz is required in the anteroposterior patterning of the pronephric progenitor domain in the intermediate mesoderm, acting in part by regulating RA signaling in the pronephric progenitor field in the intermediate mesoderm.
authors.affiliation: Leukocyte Biology & Inflammation Program, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, United States.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Leukocyte Biology & Inflammation Program, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, United States.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Leukocyte Biology & Inflammation Program, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, United States; Department of Pathology, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, United States.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Vasilyev
authors.affiliation: Leukocyte Biology & Inflammation Program, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, United States; Department of Developmental and Regenerative Biology, Harvard Medical School, Boston, MA 02115, United States. Electronic address: aarnaout1@mgh.harvard.edu.
authors.forename: M
authors.initials: M
authors.lastname: Amin Arnaout
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002452:Cell Count; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007684:Kidney Tubules / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D060910:Pronephros / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C000612287:WWTR1 protein, zebrafish; D029961:Zebrafish Proteins; D014212:Tretinoin
keywords: Kidney cysts; Patterning; Pronephros; Taz; Zebrafish