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  SLC20A1 Is Involved in Urinary Tract and Urorectal Development

Rieke, J. M., Zhang, R., Braun, D., Yilmaz, Ö., Japp, A. S., Lopes, F. M., et al. (2020). SLC20A1 Is Involved in Urinary Tract and Urorectal Development. Frontiers in Cell and Developmental Biology, 8: 567. doi:10.3389/fcell.2020.00567.

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Rieke, Johanna Magdalena , Author
Zhang, Rong, Author
Braun, Doreen, Author
Yilmaz, Öznur , Author
Japp, Anna S. , Author
Lopes, Filipa M. , Author
Pleschka, Michael , Author
Hilger, Alina C. , Author
Schneider, Sophia, Author
Newman, William G. , Author
Beaman, Glenda M. , Author
Nordenskjöld, Agneta , Author
Ebert, Anne-Karoline , Author
Promm, Martin, Author
Roesch, Wolfgang H. , Author
Stein, Raimund, Author
Hirsch, Karin, Author
Schäfer, Frank-Mattias , Author
Schmiedeke, Eberhard, Author
Boemers, Thomas M. , Author
Lacher, Martin, AuthorKluth, Dietrich , AuthorGosemann, Jan-Hendrik , AuthorAnderberg, Magnus, AuthorBarker, Gillian, AuthorHolmdahl, Gundela , AuthorLäckgren, Göran , AuthorKeene, David, AuthorCervellione, Raimondo M. , AuthorGiorgio, Elisa, AuthorDi Grazia, Massimo , AuthorWouter, Feitz F. J., AuthorMarcelis, Carlo L. M., AuthorVan Rooij, Iris A. L. M. , AuthorBökenkamp, Arend, AuthorBeckers, Goedele M. A. , AuthorKeegan, Catherine E. , AuthorSharma, Amit, AuthorChand Dakal, Tikam , AuthorWittler, Lars1, Author              Grote, Phillip , AuthorZwink, Nadine, AuthorJenetzky, Ekkehart , AuthorBrusco, Alfredo, AuthorThiele, Holger, AuthorLudwig, Michael , AuthorSchweizer, Ulrich, AuthorWoolf, Adrian S. , AuthorOdermatt, Benjamin, AuthorReutter, Heiko, Author more..
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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Free keywords: SLC20A1, urinary tract development, kidney formation, zebrafish development, cloacal malformation, functional genetics, CAKUT, bladder exstrophy-epispadias complex
 Abstract: Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.

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Language(s): eng - English
 Dates: 2020-06-152020-08-07
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3389/fcell.2020.00567
 Degree: -

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Title: Frontiers in Cell and Developmental Biology
Source Genre: Journal
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Publ. Info: Frontiers Media
Pages: - Volume / Issue: 8 Sequence Number: 567 Start / End Page: - Identifier: Other: 2296-634X
CoNE: https://pure.mpg.de/cone/journals/resource/2296-634X