Developmental Biology Laboratory: Organogenesis & Extracellular Vesicles

The underlying reseach focus in the Vainio group is organogenesis with kidney as the primary organ model. We employ novel murine and chick models along with novel biomaterials, and experiment with kidney vascularization, organoid models, and Wnt-signaling in the developing kidney.

While we are studying EVs in kidney organogenesis and skin and sensing, we also characterize EVs in other health conditions, such as cancers and brain function, and also in the nature via analysis of EVs in milk, berries, trees, and air filtrates.

We are using the skin as a model organ to detect changes in metabolism for monitoring health and disease conditions. In these projects, we use in vitro experimentation along with human skin tissue and sweat. We work with physicians and athletic team representatives in the Oulu and Northern Ostrobothnia area.

Embryogenesis is a process where the interactions between the daughter cells of the fertilized zygote pattern the embryo to generate the body plan. This general principle is also true for the control of organogenesis where the daughters of the progenitor cells, or organ stem cells go on to make the functional organs.



There is a great interest to reveal the cellular and molecular foundations of ontogenesis since impairment in the developmental control genes are typically behind several diseases such as cancer. Moreover once the details of the developmental programming is understood this knowledge can be applied to direct better for example the differentiation of the naive, multipotent cells to the specific fates and understand epigenetics in horizontal and vertical inheritance.



We have learned to generate several cell types from the naive embryonic stem cells or the so called induced pluripotent stem cells. However we still fail to construct anatomically well patterned organs from them. Once this is achieved these capacities can be expected to set the basic for novel clinical applications. Via these technologies a better use of the human population based genetic data gained from various disease types can be obtained. We should be able to couple wealth of the molecular genetic methodologies to obtain new bioengineering skills for tissue regeneration and for treatment of diseases via gene therapy when coupled to pharmacology and nanotechnology openings for example.



The focus of this research program is to increase our understanding of the fundaments of organogenesis. One of our major goals is to target the mechanisms by which the Wnt signal transduction triggers the developmental program that leads to formation of the functional of the kidney, the nephron. Certain other organs such as the heart, the gonad and the skin are also studied.

We have during the past few years developed novel ex vivo technologies to get better access to study the cellular and molecular basic of kidney organogenesis. For this purpose we have set up several gene targeted mouse models for the embryonic kidney. At present we can study in detail the major considered cell types that assemble the kidney, namely epithelial ureteric bud, nephron progenitors, stromal cells and endothelial cells. With these tools we can inactivate function of the floxed alleles in these founder cell populations.



In addition to the in vivo approaches we have gained skills to dissociate the embryonic kidney mesenchyme to single cells and yet to regenerate the potential for nephrogenesis and even the complete kidney organogenesis. We can also extend the competence window for nephrogenesis to several days ex vivo. This has given novel ways to engineer the nephron progenitor cells with viral vectors for example. Technologies are also available to silence or induce specific genes in the primary cells and to reconstitute, after such a manipulation, the potential for nephrogenesis. Moreover these engineered cells when recombined with the endogenous tubule inducer, the ureteric bud. This regenerates essentially the potential for whole kidney organogenesis.



Recently technologies have been developed where marked cells can be purified, labeled and reintroduced in to the developing organ rudiment so that cells retain their original competence. The tissue engineering capabilities and the developed mesoscopic time-lapse 3D imaging methods offer novel ways to target the nephrogenesis program. For this task we have applied the ”classic trans filter” kidney nephron induction model and identified the changes in the transcriptome in the Wnt induced MM. Several candidate developmental control genes have been identified. The major goal of our research is to reveal the detailed functions of these in the control of nephrogenesis.

The goals of our research are to gain better understanding how the cellular assemblies are set up during organogenesis. As expected the process of morphogenesis involves several cellular steps such as induced cell proliferation, cell differentiation, guided cell migration, apoptosis and changes in cell shape and adhesion between the cell and their extracellular matrix. The mechanical forces should be considered as well. We aim to identify meta level regulators and those operating in the morphogenetic field. We will target the roles of the Wnt signaling components, how they interact with the other signaling pathways such as those of the FGFs, BMPs, Notch and hedgehog. These growth factor may serve as morphogens or regulate such factors. These in turn regulate transcription factors and small RNAs. We aim to reveal new players in the organogenetic cell-cell and tissue interactions and holistic, long range signaling mechanisms to coordinate development. We look forward the opportunities of the in silico modeling and application magnetism, electronics, microfluidistics to obtain more sophisticated ex vivo technologies for generation of functional organs. The adopted technologies will used to program the naive cells to towards the renal cell lineages to gain the basic for organ engineering for human applications.