Signaling during Kidney Development

Krause, Mirja; Rak-Raszewska, Aleksandra; Pietilä, Ilkka; Quaggin, Susan E.; Vainio, Seppo

doi:10.3390/cells4020112

Cited by 54 publications

(66 citation statements)

References 121 publications

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“…Important signalling molecules such as several Wnts and Notch2 were found to be associated with EVs (summarized in [4]). Gradilla and co-workers showed that the transport of the morphogen hedgehog (Hh) is important for proper spatially restricted signalling during development [5].…”

Section: Introductionmentioning

confidence: 99%

“…Besides the survival signals, the UB also secretes signals that induce the MM to undergo nephrogenesis, such as the Wnt ligands [12–14], resulting in the development of the key functional kidney units – the nephrons [4]. While the UB is a natural MM nephrogenesis inducer, it can be removed and replaced by chemical activation of the Wnt pathway via the GSK-3 inhibitor (BIO) [15] in the process of renal organoid formation [16].…”

Section: Introductionmentioning

confidence: 99%

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Exosomes as secondary inductive signals involved in kidney organogenesis

Krause

Rak-Raszewska

Naillat

et al. 2018

J of Extracellular Vesicle

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The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also between tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species and proteins implicated in kidney development, exosomes are putative candidates to serve as developmental programming units in embryonic induction and tissue interactions. We used the mammalian metanephric kidney and its nephron-forming mesenchyme containing the nephron progenitor/stem cells as a model to investigate if secreted exosomes could serve as a novel type of inductive signal in a process defined as embryonic induction that controls organogenesis. As judged by several characteristic criteria, exosomes were enriched and purified from a cell line derived from embryonic kidney ureteric bud (UB) and from primary embryonic kidney UB cells, respectively. The cargo of the UB-derived exosomes was analysed by qPCR and proteomics. Several miRNA species that play a role in Wnt pathways and enrichment of proteins involved in pathways regulating the organization of the extracellular matrix as well as tissue homeostasis were identified. When labelled with fluorescent dyes, the uptake of the exosomes by metanephric mesenchyme (MM) cells and the transfer of their cargo to the cells can be observed. Closer inspection revealed that besides entering the cytoplasm, the exosomes were competent to also reach the nucleus. Furthermore, fluorescently labelled exosomal RNA enters into the cytoplasm of the MM cells. Exposure of the embryonic kidney-derived exosomes to the whole MM in an ex vivo organ culture setting did not lead to an induction of nephrogenesis but had an impact on the overall organization of the tissue. We conclude that the exosomes provide a novel signalling system with an apparent role in secondary embryonic induction regulating organogenesis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exosomes as secondary inductive signals involved in kidney organogenesis

Krause

Rak-Raszewska

Naillat

et al. 2018

J of Extracellular Vesicle

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“…54 EMT, for instance, has been described in the kidney, liver, and pancreas of mammals during early embryonic development. [55][56][57][58] Similar pathways are present in carcinomas of various organs where L1CAM converts epithelial cells into a migrating phenotype via the stimulation of the beta-catenin pathway and inhibition of adherens junction formation. 59 Moreover, abolition of the cell-cell contacts is triggered by a cleavage Editor's Highlight of the L1CAM ectodomain via the metalloproteinases ADAM 10 and 17.…”

Section: Discussionmentioning

confidence: 96%

L1CAM in the Early Enteric and Urogenital System

Pechriggl

Concin

Blumer

et al. 2016

J Histochem Cytochem.

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Article IntroductionIn 1984, Rathjen and Schachner identified a new cell adhesion molecule (L1 cell adhesion molecule [L1CAM]) in neurons that turned out to be a key player in the neuronal development of mice where it governs neuronal outgrowth, migration, and axonal guidance. 1 L1CAM is a transmembrane protein belonging to the immunoglobulin superfamily, interacting with several ligands such as integrins, neuropilins, contactin 1 and 2, CD24, as well as with its shed form. 2Apart from its established function, studies in rodents and cell lines showed that L1CAM has an essential role in the formation and maintenance of epithelia, which is achieved via two contrary modes of action: On the one hand, L1CAM is important for both the establishment of cell-cell complexes and the SummaryL1 cell adhesion molecule (L1CAM) is a transmembrane molecule belonging to the L1 protein family. It has shown to be a key player in axonal guidance in the course of neuronal development. Furthermore, L1CAM is also crucial for the establishment of the enteric and urogenital organs and is aberrantly expressed in cancer originating in these organs. Carcinogenesis and embryogenesis follow a lot of similar molecular pathways, but unfortunately, comprehensive data on L1CAM expression and localization in human developing organs are lacking so far. In the present study we, therefore, examined the spatiotemporal distribution of L1CAM in the early human fetal period (weeks 8-12 of gestation) by means of immunohistochemistry and in situ hybridization (ISH). In the epithelia of the gastrointestinal organs, L1CAM localization cannot be observed in the examined stages most likely due to their advanced polarization and differentiation. Despite these results, our ISH data indicate weak L1CAM expression, but only in few epithelial cells. The genital tracts, however, are distinctly L1CAM positive throughout the entire fetal period. We, therefore, conclude that in embryogenesis L1CAM is crucial for further differentiation of epithelia. (J Histochem Cytochem 65:21-32, 2017)

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“…As a result, epithelial stem cells in the tip of a CD ampulla meet GDNF + /Six2 + /CITED1 + mesenchymal cells [51, 52]. At the same time, a reciprocal exchange of morphogens within the niche takes place [37, 38]. When the signaling for the process of induction is successful, a few mesenchymal cells separate, aggregate, and perform a mesenchyme-to-epithelial transition (MET) to develop into a renal vesicle at the lateral aspect of the related CD ampulla [63].…”

Section: Fine Positioning Of Stem Cellsmentioning

confidence: 99%

“…Initiated by branching morphogenesis, it shows a radial and, at the same time, fan-like extension [32-36]. On the other hand, intact development of nephrons principally presupposes successive interactions between branches of the ureteric bud and facing mesenchymal stem cells [37, 38]. …”

Section: Eccentric Position Of the Nephrogenic Zonementioning

confidence: 99%

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

Minuth¹

2017

Nephron

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While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches.

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Signaling during Kidney Development

Cited by 54 publications

References 121 publications

Exosomes as secondary inductive signals involved in kidney organogenesis

Exosomes as secondary inductive signals involved in kidney organogenesis

L1CAM in the Early Enteric and Urogenital System

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

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