title: Wnt8a expands the pool of embryonic kidney progenitors in zebrafish.
abstract: During zebrafish embryogenesis the pronephric kidney arises from a small population of posterior mesoderm cells that then undergo expansion during early stages of renal organogenesis. While wnt8 is required for posterior mesoderm formation during gastrulation, it is also transiently expressed in the post-gastrula embryo in the intermediate mesoderm, the precursor to the pronephros and some blood/vascular lineages. Here, we show that knockdown of wnt8a, using a low dose of morpholino that does not disrupt early mesoderm patterning, reduces the number of kidney and blood cells. For the kidney, wnt8a deficiency decreases renal progenitor growth during early somitogenesis, as detected by EdU incorporation, but has no effect on apoptosis. The depletion of the renal progenitor pool in wnt8a knockdown embryos leads to cellular deficits in the pronephros at 24 hpf that are characterised by a shortened distal-most segment and stretched proximal tubule cells. A pulse of the canonical Wnt pathway agonist BIO during early somitogenesis is sufficient to rescue the size of the renal progenitor pool while longer treatment expands the number of kidney cells. Taken together, these observations indicate that Wnt8, in addition to its well-established role in posterior mesoderm patterning, also plays a later role as a factor that expands the renal progenitor pool prior to kidney morphogenesis.
authors.affiliation: Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1142, New Zealand. Electronic address: r.naylor@auckland.ac.nz.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Naylor
authors.affiliation: Department of Developmental Biology, Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: hih9@pitt.edu.
authors.forename: Hwa In
authors.initials: HI
authors.lastname: Han
authors.affiliation: Department of Developmental Biology, Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: hukriede@pitt.edu.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hukriede
authors.affiliation: Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1142, New Zealand. Electronic address: a.davidson@auckland.ac.nz.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Davidson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects; D019521:Body Patterning / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000166:cytology* / Q000196:embryology*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008648:Mesoderm / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D060172:Morpholinos / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D060910:Pronephros / Q000166:cytology / Q000196:embryology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C483321:6-bromoindirubin-3'-oxime; D003598:Cytoskeletal Proteins; D007211:Indoles; D060172:Morpholinos; D010091:Oximes; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C094521:wnt8a protein, zebrafish
keywords: Intermediate mesoderm; Proliferation; Pronephros; Wnt8; Zebrafish