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Cells
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Normal and Deregulated Coordination of the Kidney Gonadal Axis by...
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Normal and Deregulated Coordination of the Kidney Gonadal Axis by the Wnts

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 21570

Special Issue Editors

Prof. Dr. Seppo Vainio

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Guest Editor
Biocenter Oulu, Laboratory of Developmetnal Biology, Faculty of Biochemistry and Molecular Medicine, Borealis Biobank of Northern Finland, InfoTech, University of Oulu, Oulu, Finland
Interests: inductive signaling; control of cell fate; regeneration; morphogenesis; reprogramming
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Florence Naillat

E-Mail Website
Guest Editor
Biocenter Oulu, Laboratory of Developmental Biology, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Interests: reproductive organs; germ cells; epigenetics; metabolism; kidneys
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the animal kingdom, Wnt signaling is involved in the development of the body plan throughout the life cycle. The Wnt pathway is complex and diverse. When the Wnt signal activates its receptor, the response is chosen from three options: the canonical Wnt pathway that drives β-catenin to the nucleus, activating gene expression; the non-canonical pathway that remodels the cell cytoskeleton via planar cell polarity; and the Wnt/Calcium pathway that controls intracellular calcium.

Wnt signaling is implicated in embryonic development and, more specifically, the development of the urogenital system during kidney development and sex differentiation. In adulthood in healthy processes, Wnt signaling is involved in the regeneration of the kidney stem cells, whereas dysfunction of the Wnt pathway often leads to a number of pathological conditions, such as acute/chronic kidney injuries, cystic kidneys, renal carcinoma, and reproductive organ cancer.

In this Special Issue of Cells, we invite contributions in the form of original research articles, reviews, or shorter perspective articles on all aspects related to the theme of “Wnt signaling in kidney and sex organ diseases”. Articles with mechanistic and functional insights from an organ and disease or a molecular biological perspective are especially welcome. Relevant topics include, but are not limited to:

  • Wnt signaling and kidney development
  • Wnt and kidney diseases
  • Wnt signaling and reproductive organ development
  • Wnt and reproductive organ diseases
  • Wnt signaling and environmental impact
  • Wnt and cancer
  • Therapeutic implication in Wnt-associated diseases

Prof. Seppo Vainio
Dr. Florence Naillat
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • kidney injury
  • urogenital system
  • Wnt signaling
  • extracellular vesicles (EVs)
  • cancer
  • treatments
  • reproductive organs

Published Papers (2 papers)

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Research

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18 pages, 15369 KiB  
Article
Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9
by Furong Tang, Nainoa Richardson, Audrey Albina, Marie-Christine Chaboissier and Aitana Perea-Gomez
Cells 2020, 9(5), 1103; https://doi.org/10.3390/cells9051103 - 29 Apr 2020
Cited by 12 | Viewed by 5309
Abstract
The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal [...] Read more.
The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when Sox9 and Wnt4 are both mutated. We show that the XX gonad mutant for Wnt4 or for both Wnt4 and Sox9 develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a Wnt4 mutation. Sox9 deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/β-catenin signaling. In XY Sox9 mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of Wnt4 or Rspo1, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/β-Catenin signaling. However, in XY Sox9 Wnt4 double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation. Full article
(This article belongs to the Special Issue Normal and Deregulated Coordination of the Kidney Gonadal Axis by the Wnts)
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Review

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20 pages, 1821 KiB  
Review
Kidney Organoids and Tubuloids
by Fjodor A. Yousef Yengej, Jitske Jansen, Maarten B. Rookmaaker, Marianne C. Verhaar and Hans Clevers
Cells 2020, 9(6), 1326; https://doi.org/10.3390/cells9061326 - 26 May 2020
Cited by 50 | Viewed by 15775
Abstract
In the past five years, pluripotent stem cell (PSC)-derived kidney organoids and adult stem or progenitor cell (ASC)-based kidney tubuloids have emerged as advanced in vitro models of kidney development, physiology, and disease. PSC-derived organoids mimic nephrogenesis. After differentiation towards the kidney precursor [...] Read more.
In the past five years, pluripotent stem cell (PSC)-derived kidney organoids and adult stem or progenitor cell (ASC)-based kidney tubuloids have emerged as advanced in vitro models of kidney development, physiology, and disease. PSC-derived organoids mimic nephrogenesis. After differentiation towards the kidney precursor tissues ureteric bud and metanephric mesenchyme, their reciprocal interaction causes self-organization and patterning in vitro to generate nephron structures that resemble the fetal kidney. ASC tubuloids on the other hand recapitulate renewal and repair in the adult kidney tubule and give rise to long-term expandable and genetically stable cultures that consist of adult proximal tubule, loop of Henle, distal tubule, and collecting duct epithelium. Both organoid types hold great potential for: (1) studies of kidney physiology, (2) disease modeling, (3) high-throughput screening for drug efficacy and toxicity, and (4) regenerative medicine. Currently, organoids and tubuloids are successfully used to model hereditary, infectious, toxic, metabolic, and malignant kidney diseases and to screen for effective therapies. Furthermore, a tumor tubuloid biobank was established, which allows studies of pathogenic mutations and novel drug targets in a large group of patients. In this review, we discuss the nature of kidney organoids and tubuloids and their current and future applications in science and medicine. Full article
(This article belongs to the Special Issue Normal and Deregulated Coordination of the Kidney Gonadal Axis by the Wnts)
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