Satu Kuure

Satu Kuure
University of Helsinki | HY · Medicum

PhD

About

57
Publications
6,340
Reads
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1,521
Citations
Additional affiliations
February 2011 - present
University of Helsinki
Position
  • Researcher
September 2007 - December 2009
Columbia University
Position
  • PostDoc Position
September 1995 - February 1996
University of Oulu
Position
  • trainee
Description
  • Master's thesis

Publications

Publications (57)
Article
Full-text available
Background MAPK/ERK signaling is a well-known mediator of extracellular stimuli controlling intracellular responses to growth factors and mechanical cues. The critical requirement of MAPK/ERK signaling for embryonic stem cell maintenance is demonstrated, but specific functions in progenitor regulation during embryonic development, and in particular...
Preprint
Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at the branch points. Nephrons form in the cap mesenchyme as the metanephric mesenchyme (MM) condenses around the epithelial ureteric buds (UBs). Previous work demonstrated that FGF8 is important for the survival of nephron progenitor cells (NPCs),...
Article
Full-text available
The modification of genes in animal models has evidently and comprehensively improved our knowledge on proteins and signaling pathways in human physiology and pathology. In this review, we discuss almost 40 monogenic rare diseases that are enriched in the Finnish population and defined as the Finnish disease heritage (FDH). We will highlight how ge...
Preprint
Nephron endowment is defined by fetal kidney growth and it critically dictates renal health in adults. Despite the advances in understanding the molecular regulation of nephron progenitor maintenance, propagation, and differentiation, the causes for low congenital nephron count and contribution of basic metabolism to nephron progenitor regulation r...
Article
Full-text available
Transforming growth factor-beta (TGFβ) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGFβ activity by acting as a storage compartment of latent-TGFβ, but how TGFβ is released from the ECM via proteolytic...
Article
Full-text available
Nephron endowment, defined during the fetal period, dictates renal and related cardiovascular health throughout life. We show here that, despite its negative effects on kidney growth, genetic increase of GDNF prolongs the nephrogenic program beyond its normal cessation. Multi-stage mechanistic analysis revealed that excess GDNF maintains nephron pr...
Article
Full-text available
The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) ne...
Article
Full-text available
The 16th transgenic technology (TT) meeting of the International Society of Transgenic technology (ISTT) took place on October 26–29th 2020 and was quite unique as it was the first-ever virtual meeting in the history of ISTT events. Dr. Rebecca Haffner-Krausz at Weizmann Institute of Science, Israel, was the local organizer of the meeting, which at...
Preprint
Full-text available
Due to poor regenerative capacity of adult kidneys, nephron endowment defined by the nephrogenic program during the fetal period dictates renal and related cardiovascular health throughout life. We show that the neurotropic factor GDNF, which is in clinical trials for Parkinson's disease, is capable of prolonging the nephrogenic program beyond its...
Chapter
Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects, which cause the majority of chronic kidney diseases in children. CAKUT covers a wide range of malformations that derive from deficiencies in embryonic kidney and lower urinary tract development, including renal aplasia, hypodysplasia, hypoplasia, ectopia, and dif...
Article
Full-text available
The demand for single-cell level data is constantly increasing within life sciences. In order to meet this demand, robust cell segmentation methods that can tackle challenging in vivo tissues with complex morphology are required. However, currently available cell segmentation and volumetric analysis methods perform poorly on 3D images. Here, we gen...
Article
Full-text available
Kidney mesenchyme (KM) and nephron progenitors (NPs) depend on WNT activity, and their culture in vitro requires extensive repertoire of recombinant proteins and chemicals. Here we established a robust, simple culture of mouse KM using a combination of 3D Matrigel and growth media supplemented with Fibroblast Growth Factor 2 (FGF2) and Src inhibito...
Article
Full-text available
Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects derived from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding o...
Article
Full-text available
Mechanisms controlling ureter lenght and the position of the kidney are poorly understood. Glial cell-line derived neurotrophic factor (GDNF) induced RET signaling is critical for ureteric bud outgrowth, but the function of endogenous GDNF in further renal differentiation and urogenital system development remains discursive. Here we analyzed mice w...
Preprint
Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects deriving from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding...
Article
FAT4 mutations lead to several human diseases that disrupt the normal development of the kidney. However, the underlying mechanism remains elusive. In studying the duplex kidney phenotypes observed upon deletion of Fat4 in mice, we have uncovered an interaction between the atypical cadherin FAT4 and RET, a tyrosine kinase receptor essential for kid...
Chapter
Full-text available
Kidney organogenesis has been a widely used classical model system to study inductive tissue interactions that guide differentiation of many organs. The basis for this is in the pioneering work done during the early 1950s when the conditions of how to support ex vivo growth and differentiation of developing kidneys were revealed. Importantly, cultu...
Article
Full-text available
Classically, trophic factors are considered as proteins which support neurons in their growth, survival, and differentiation. However, most neurotrophic factors also have important functions outside of the nervous system. Especially essential renal growth and differentiation regulators are glial cell line-derived neurotrophic factor (GDNF), bone mo...
Data
Video S2. Live-Imaging of FRET Biosensor for ERK Activation in FGF2-Treated E12.5 Kidney (315 min)
Data
Video S1. Live-Imaging of FRET Biosensor for ERK Activation in E12.5 Kidney (480 min)
Data
Video S4. Live-Imaging of Sphere Formation in Dissociated Nephron Progenitors Treated with FGF2 (24 hr)
Data
Video S3. Live-Imaging of FRET Biosensor for ERK Activation in MEK-Inhibited E12.5 Kidney (590 min)
Article
Full-text available
The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Fo¨rster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiati...
Article
Full-text available
STATEMENT Both plasticity and genetic variation in kidney morphology and candidate gene expression have likely facilitated adaptation to permanent low salinity residency in threespine stickleback populations from the Baltic Sea. ABSTRACT Novel physiological challenges in different environments can promote the evolution of divergent phenotypes, eith...
Article
In Parkinson's disease midbrain dopaminergic neurons degenerate and die. Oral medications and deep brain stimulation can relieve the initial symptoms, but the disease continues to progress. Growth factors that might support the survival, enhance the activity, or even regenerate degenerating dopamine neurons have been tried with mixed results in pat...
Article
Full-text available
Degeneration of nigrostriatal dopaminergic system is the principal lesion in Parkinson's disease. Because glial cell line-derived neurotrophic factor (GDNF) promotes survival of dopamine neurons in vitro and in vivo, intracranial delivery of GDNF has been attempted for Parkinson's disease treatment but with variable success. For improving GDNF-base...
Article
Full-text available
The pluripotency and self-renewal capacity of embryonic stem (ES) cells is regulated by several transcription factors. Here, we show that the ETS-related transcription factors ETV4 and ETV5 (ETV4/5) are specifically expressed in undifferentiated ES cells, and suppression of Oct3/4 results in down-regulation of ETV4/5. Simultaneous deletion of ETV4...
Article
Full-text available
Although the growth factor (GF) signaling guiding renal branching is well characterized, the intracellular cascades mediating GF functions are poorly understood. We studied mitogen-activated protein kinase (MAPK) pathway specifically in the branching epithelia of developing kidney by genetically abrogating the pathway activity in mice lacking simul...
Article
Full-text available
Kidney development has been widely used as a model system to study molecular control of inductive tissue interactions and mechanisms through which branching organs form. Due to lacking or poor methods, less focus has been in understanding details of cellular events that accomplish example ureteric bud (UB) branching. In order to form a branch point...
Article
Full-text available
Glial cell line-derived neurotrophic factor (GDNF) is indispensable for ureteric budding and branching. If applied exogenously, GDNF promotes ectopic ureteric buds from the Wolffian duct. Although several downstream effectors of GDNF are known, the identification of early response genes is incomplete. Here, microarray screening detected several GDN...
Article
Branching morphogenesis is a central developmental mechanism utilized in the morphogenesis of several organs including lung, liver, salivary gland and kidney. The molecular control of the basic process of renal differentiation, the ureteric bud (UB) branching, has been in the focus of extensive studies while the cellular events, such as migration a...
Article
The tip of the ureteric bud in the metanephric kidney is a signaling center inducing formation of mesenchyme-derived nephrons, and simultaneously it responds by growth and branching to signals from the mesenchyme. Here we report that Visinin like 1 (Vsnl1) is a new ureteric bud tip marker, which encodes for a neuronal calcium sensor—Vsnl1 protein w...
Article
Signaling by GDNF through the Ret receptor tyrosine kinase is required for the normal formation, growth and branching of the ureteric bud (UB) during kidney development. However, the precise role of GDNF/Ret signaling in this process, and the specific responses of UB cells to GDNF, remain to be fully elucidated. Recent studies provide new insight i...
Data
Double ureters in Dstn-/- and delayed UB branching in Cfl1+/-;Dstn-/- embryos. (A-B), double ureter (arrows) in a Dstn-/- embryo (B) compared to single ureter in control (A), at E11.5. (C-F), Hoxb7/myrVenus transgene expressed in ureteric bud epithelium reveals slightly delayed branching morphogenesis in a Cfl1+/-;Dstn-/- kidney at E12.5. C and E,...
Data
Establishment of primary UB cell cultures. Ureteric buds were isolated free of metanephric mesenchyme and plated in fibronectin coated wells, where they attach and form monolayers. (A), Primary ureteric epithelial cells of all genotypes (Dstn+/- is shown) were relatively quiescent in culture, as shown by the paucity of Ki67+ (green) proliferative c...
Data
F-actin distribution is normal in double mutant Wolffian duct at E10.5. Embryos were stained for phalloidin (red) to visualize F-actin and for calbindin (green) to demarcate the Wolffian duct and ureteric bud epithelium. (A), Wild type embryo. (A') shows higher magnification of F-actin distribution in wild type Wolffian duct. F-actin remains normal...
Data
Normal expression of Ret and Wnt11 in Cfl1;Dstn double mutant UBs. (A-D) Control and double mutant kidneys at E11.5 (A, B) or E11.5+18hrs of culture (C, D) were used for Ret whole mount in situ hybridization. (A) control (no Cre; Cfl1F/+; Dstn-/-), (B) double mutant. The UBs are demarcated by dotted lines. (C) control (Hoxb7/CreGFP; Cfl1+/+; Dstn+/...
Article
Full-text available
The actin depolymerizing factors (ADFs) play important roles in several cellular processes that require cytoskeletal rearrangements, such as cell migration, but little is known about the in vivo functions of ADFs in developmental events like branching morphogenesis. While the molecular control of ureteric bud (UB) branching during kidney developmen...
Article
Full-text available
Signaling by the Ret receptor tyrosine kinase promotes cell movements in the Wolffian duct that give rise to the first ureteric bud tip, initiating kidney development. Although the ETS transcription factors Etv4 and Etv5 are known to be required for mouse kidney development and to act downstream of Ret, their specific functions are unclear. Here, w...
Article
Full-text available
Glial cell line-derived neurotrophic factor signaling through the Ret receptor tyrosine kinase is crucial for ureteric bud branching morphogenesis during kidney development, yet few of the downstream genes are known. Here we show that the ETS transcription factors Etv4 and Etv5 are positively regulated by Ret signaling in the ureteric bud tips. Mic...
Article
WNT/beta-catenin signaling has an established role in nephron formation during kidney development. Yet, the role of beta-catenin during ureteric morphogenesis in vivo is undefined. We generated a murine genetic model of beta-catenin deficiency targeted to the ureteric bud cell lineage. Newborn mutant mice demonstrated bilateral renal aplasia or ren...
Article
Full-text available
The most severe forms of motoneuron disease manifest in utero are characterized by marked atrophy of spinal cord motoneurons and fetal immobility. Here, we report that the defective gene underlying lethal motoneuron syndrome LCCS1 is the mRNA export mediator GLE1. Our finding of mutated GLE1 exposes a common pathway connecting the genes implicated...
Article
Full-text available
Wnt proteins are required for induction of nephrons in mouse metanephric kidneys, but the downstream pathways that mediate tubule induction and epithelial differentiation have remained obscure. The intracellular mechanisms by which Wnt signaling mediates nephron induction in embryonic kidney mesenchymes were studied. First is shown that transient e...
Article
Glial-Cell-Line-Derived Neurotrophic Factor (GDNF) is the major mesenchyme-derived regulator of ureteric budding and branching during nephrogenesis. The ligand activates on the ureteric bud epithelium a receptor complex composed of Ret and GFRalpha1. The upstream regulators of the GDNF receptors are poorly known. A Notch ligand, Jagged1 (Jag1), co-...
Article
Development of an organ is directed by cell and tissue interactions and these also occur during the formation of functional kidney. During vertebrate development inductive signalling between mesenchyme and epithelium controls the organogenesis of all three kinds of kidneys: pronephros, mesonephros and metanephros. In higher animals the metanephros...
Article
Members of the human cytochrome P450 2A (CYP2A) subfamily are known to metabolize several promutagens, procarcinogens, and pharmaceuticals. In this study, the expression of the three genes found in the human CYP2A gene cluster was investigated in the liver and several extrahepatic tissues by gene-specific reverse transcriptase-polymerase chain reac...
Article
Full-text available
The permanent mammalian kidney (metanephros) develops as a result of complex reciprocal tissue interactions between a ureteric epithelium and the renal mesenchyme. The overall goal of the research in this thesis was to gain data that will eventually help in elucidating the formation of congenital renal malformations. The experiments in my thesis ai...

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