- Renal and related cancers
- Reproductive Biology and Fertility
- Renal cell carcinoma treatment
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Wnt/β-catenin signaling in development and cancer
- Urological Disorders and Treatments
- Tissue Engineering and Regenerative Medicine
- Organ Donation and Transplantation
- Sexual Differentiation and Disorders
- Ovarian function and disorders
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Genetic and Kidney Cyst Diseases
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Sperm and Testicular Function
- Reproductive Health and Technologies
- Extracellular vesicles in disease
- Congenital Diaphragmatic Hernia Studies
- Reproductive System and Pregnancy
- Testicular diseases and treatments
- Fibroblast Growth Factor Research
University of Oulu
2011-2024
Biocenter Finland
2022
Babraham Institute
2021
Research Council of Finland
2015
Matrix Research (United States)
2010
Wellcome Centre for Cell-Matrix Research
2010
To bypass the essential gastrulation function of Fgf8 and study its role in lineages primitive streak, we have used a new mouse line, T-Cre, to generate embryos with pan-mesodermal loss expression. Surprisingly, despite previous models which has been assigned pivotal segmentation/somite differentiation, is not required for these processes. However, mutant neonates display severe renal hypoplasia deficient nephron formation. In kidneys, aberrant cell death occurs within metanephric mesenchyme...
Antagonists act to restrict and negatively modulate the activity of secreted signals during progression embryogenesis. In mouse embryos lacking extra-cellular BMP antagonist gremlin 1 (Grem1), metanephric development is disrupted at stage initiating ureteric bud outgrowth. Treatment mutant kidney rudiments in culture with recombinant protein induces additional epithelial buds restores outgrowth branching. All express Wnt11, Gdnf significantly upregulated surrounding mesenchyme, indicating...
Germ cells are the foundation of an individual, since they generate gametes and provide unique genome established through meiosis. The sex-specific fate germline in mammals is thought to be controlled by somatic signals, which still poorly characterized. We demonstrate here that Wnt signalling crucial for control female development. Wnt-4 maintains germ cell cysts early follicular gene expression provides a pattern E-cadherin β-catenin within cells. In addition, we find Stra8 downregulated...
Wnt-4 signaling has been implicated in female development, because its absence leads to partial male sex reversal the mouse. Instead of Mullerian ducts, Wnt-4-deficient females have Wolffian suggesting a role for androgens maintaining this single-sex duct type females. We demonstrate here that testosterone is produced by ovary embryos and also detected embryonic plasma. Consistent with this, expression several genes encoding enzymes pathway leading synthesis mouse induced ovary, including...
ErbB4 receptor tyrosine kinase contributes to the development of heart, central nervous system, and lactating mammary gland, but whether it has a role in kidney epithelium is unknown. Here, we found that expression Erbb4 isoforms JM-a CYT-1 CYT-2 was first detectable around embryonic day 13 mouse, mainly collecting ducts both proximal distal tubules. In vitro, overexpression relevant isoform promoted proliferation disturbed polarization epithelial cells when cultured as three-dimensional...
The indifferent mammalian embryonic gonad generates an ovary or testis, but the factors involved are still poorly known. Wnt-4 signal represents one critical female determinant, since its absence leads to partial female-to-male sex reversal in mouse, signalling is as well implicated testis development. We used deficient mouse a model identify candidate gonadogenesis genes, and found that Notum, Phlda2, Runx-1 Msx1 genes typical of wild-type Osr2, Dach2, Pitx2 Tacr3 testis. Strikingly,...
ABSTRACT The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species proteins implicated in kidney development, exosomes are putative candidates serve developmental programming units embryonic induction tissue interactions. We used the mammalian metanephric its nephron‐forming mesenchyme containing...
Collagen XVIII (ColXVIII) is a component of the extracellular matrix implicated in embryogenesis and control tissue homoeostasis. We now provide evidence that ColXVIII has specific role renal branching morphogenesis as observed analyses total isoform-specific knockout embryos mice. The expression short two longer isoforms differ temporally spatially during development. lack or its lead to congenital defects 3D patterning ureteric tree where isoform plays prominent role. Moreover, ex vivo...
Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders leading to infertility in women affecting reproductive, and metabolic systems. Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) ERBB4 receptor tyrosine kinase 4 gene, but its role development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all reproductive features are available, we conditionally deleted...
Abstract Background Wnt11 is a member of the Wnt family secreted signals controlling early steps in ureteric bud (UB) branching. Due to reported lethality knockout embryos utero , its role later mammalian kidney organogenesis remains open. The presence emerging tubular system suggests that it may have certain roles development epithelial ductal system. Results allele was backcrossed with C57Bl6 strain for several generations address possible differences penetrance phenotypes. Strikingly,...
Reproductive biology methods rely on in vitro follicle cultures from mature follicles obtained by hormonal stimulation for generating metaphase II oocytes to be fertilised and developed into a healthy embryo. Such techniques are used routinely both rodent human species. DNA methylation is dynamic process that plays role epigenetic regulation of gametogenesis development. In mammalian oocytes, establishment regulates gene expression the embryos. This particularly important class genes,...
Renal development is a complex process in which two major processes, tubular branching and nephron development, regulate each other reciprocally. Our previous findings have indicated that collagen XVIII (ColXVIII), an extracellular matrix protein, affects the renal morphogenesis. We investigate here role of ColXVIII formation behavior progenitor cells (NPCs) using isoform-specific knockout mice. The results show short isoform predominates early epithelialized structures whereas longer...
Although close to every fifth couple nowadays has difficulty conceiving, the molecular mechanisms behind decline in human reproduction remain poorly understood. We report here that receptor tyrosine kinase Erbb4 is a candidate causal gene, because it expressed sexually dimorphic manner and abundant developing adult testes mouse. Sertoli cell-specific Erbb4-knockout mice have compromised 3-dimensional organization of testicular seminiferous tubules affects their fertility. More specifically,...
Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at branch points. Nephrons form in cap mesenchyme as metanephric (MM) condenses around buds (UBs). Previous work has demonstrated that FGF8 is important for survival nephron progenitor cells (NPCs), early deletion Fgf8 leads to cessation formation, which results post-natal lethality. We now reveal a previously unreported function FGF8. By combining transgenic mouse models, quantitative...
Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at branch points. Nephrons form in cap mesenchyme as metanephric (MM) condenses around buds (UBs). Previous work demonstrated that FGF8 is important for survival nephron progenitor cells (NPCs), early deletion Fgf8 leads to cessation formation, which results post-natal lethality. We now reveal a novel function FGF8. By combining transgenic mouse models, quantitative imaging assays,...
Tissue organoids derived from primary cells have high potential for studying organ development and diseases in numerous organs. They recreate the morphological structure mimic functions of given while being compact size, easy to produce, suitable use various experimental setups.In this study we established number that form mouse kidney rudiments at E11.5, generated renal sizes metanephric mesenchyme (MM). We investigated ability undergo nephrogenesis upon Wnt/ β-catenin pathway-mediated...
The renal tubular epithelial cells (TEC) have a strong capacity for repair after acute injury, but when this mechanism becomes uncontrollable, it leads to chronic kidney diseases (CKD). Indeed, in progress toward CKDs, the TECs may dedifferentiate, undergo epithelial-to-mesenchyme transition (EMT), and promote inflammation fibrosis. Given critical role of Wnt4 signaling ontogenesis, we addressed whether changes are connected fibrosis by taking advantage knock-in Wnt4mCh/mCh mouse. While...
In the last four decades, transgenic and knockout mouse models have helped to understand mechanisms of mammalian sex determination, germ cell development, adult gonad functions. We gained crucial insights into molecular factors pathways cells generating either supporting gonadal or both sexes. this review, we highlighted some main gene networks regulatory involved in plasticity sex-determining that help establish a functional ovary can nurture follicles generate good ovarian reserve,...