Developmental biology and regenerative medicine
Our group is known for running many, sometimes seemingly disconnected, projects. This is happening because we mainly aim at discovering new principles rather than factological details.
We do have our own scientific philosophy and we respect theoretical biology in addition to classical experimental approach. We look at a range of live systems from a mechanistic point of view, trying to decompose and reverse engineer different parts or aspects of life. Tracing the incremental advancements in development of multicellular organisms from single cell allows understanding the complexity of the entire organism or organ system in a final phase. That is why our main strength is developmental biology. The knowledge gained from developmental biology research is widely applied in regenerative medicine, and, thus, we hope to improve human health via discovering new fundamental ideas about how regeneration works.
I am a classical developmental biologist who started to engage into regenerative medicine. Currently my work is concentrated on different aspects of stem cell biology. I am generally interested in understanding numerous principles of animal design. To be more detailed, I try to focus on cellular aspects of development and evolution, elaboration of novelties in cellular lineages, issues of biological individuality and competition of cells inside of the multicellular organisms.
Today the following biological questions hit the top of my list:
- Peripheral glial cells as a multipotent source of building blocks within the innervated tissues, both during development and regeneration.
- Control of regeneration in vertebrates, reception of local damage by surrounding tissue.
- Evolution of differentiated cell types, elaboration of novel functional properties in cellular lineages.
- Understanding the molecular basis of body plan evolution in connection with different types of embryonic development and early lineage plasticity.
Viacheslav Dyachuk, PhD, Postdoc
My current projects are focused around the formation of the parasympathetic nervous system during development. This is an interesting topic because many organs in our body develop during relatively late stages of embryogenesis, for example, salivary and lacrimal glands, urinary bladder, gonads, lungs and many more. These organs are innervated by parasympathetic neurons that are positioned close to their targets, somewhere deep in the body. How these neurons appear at the locations associated with very late development and so distant from CNS?
The goal of the present project is to find the sources of precursors of parasympathetic neurons and discover the mechanism of their differentiation in development. Recently we have shown that parasympathetic neurons arise from Schwann cell precursors (SCP) – embryonic glial cells residing in peripheral nerves. These nerves travel everywhere in the body targeting every peripheral tissue or organ since early developmental stages. Using multi-color genetic tracing and transgenic mice we demonstrated that SCPs are able to generate both parasympathetic neurons and mature myelinating and non-myelinating glia. We proved the importance of preganglionic motor nerves in delivering glial progenitors to the sites of parasympathetic neurogenesis. Discovered phenomenon raises many interesting biological questions that we are currently addressing. For example, what are the signals that recruit SCPs from nerves and dictate the precise location of parasympathetic ganglia? How the number of parasympathetic neurons is controlled? How maturing parasympathetic ganglia and postganglionic fibers govern the development of target organs? Additionally, we are looking for signals that would explain the molecular mechanisms of neuro-glial communication during development.
Kaj Fried, PhD, Professor, close collaborator, honored associated member
Kaj Fried has a long-standing experience from studies of the development and trigeminal innervation of teeth. Over the years Kaj investigated an array of various dental nerve-target interactions, with focus on developmental processes. Special emphasis has been given to the neural molecular factors at early stages of tooth organogenesis. In years 2009–2012 Kaj Fried was a Head of Department, Department of Dental Medicine, Karolinska Institutet. In 1998 he has received IADR (International Association for Dental Research) Pulp Biology Research Award. During 2002–2006 he was a representative from Sweden within the framework for the COST B23 EU collaboration on Tooth Morphology and Differentiation, and Chairman of the Workgroup on Stem cells and Tissue regeneration (2003–2006). Currently Kaj is supervising a number of projects that our laboratories run together. These projects are mostly related to the development of craniofacial innervation and the role of the peripheral nerve in tooth organogenesis. Apparently, from time to time Kaj comes to the bench to run challenging experiments and to demonstrate how the proper wet lab science must be done, especially when it comes to complicated microsurgery. Kaj Fried is a close collaborator, advisor, fantastic person and a good friend of our lab.
Marketa Kaucka, PhD, Postdoc, EMBO Fellow
Every week new articles about how the shape of the face influences one's life, relationships and success appear in the magazines. Beautiful faces of models look down at us from posters and advertisements and billions of people all over the world undergo plastic surgeries and use make-up to improve their visage. When you want to travel, there is a picture of your face in the passport to prove your identity. Every person carries unique features in the face that make him/her different from the others and the uniqueness is given by the shape of the skull.
Despite we all differ from each other significantly, we all still have a nose, ears, jaws and very special structures inside of the head such as inner ear and olfactory system. As a matter of evolution, the skull with all fine structures arose in order to protect sensitive organs of nervous system and thus they are protected first with hard matrix – bone. All the structures forming the face and the cranium are neural-crest derived and are created at the first step during embryogenesis by the cartilage and later are replaced by the bone. The whole process is genetically conserved not only in human but also among many other species. The development of the cartilage and bone is very tightly regulated but still, there is a space for being different from the others. A lot of effort has been invested in defining the key regulators of craniofacial development and many genes and signaling pathways have been linked to specific pathologies and abnormalities. Most of the published work simply relates certain phenotype to certain gene without knowing what specifically is influenced. Is it inability of the cells to migrate or divide? Are the survival or differentiation factors missing? My aim is to investigate what happens in between the disruption of the gene and the subsequent pathology. Why e.g. the mutants of Wnt/PCP pathway have shortened snout, what is the cell dynamics behind the processes of cartilage and bone formation.
I would like to understand what makes the cartilage occur in defined distance from the nerve tissues, how it later expands and elongates, what cells are dividing in order to increase the volume, how the shape of the structures is regulated and built and if there are “stem cells” later in the adulthood that serve for the purpose of bone remodeling and regeneration.
In summary, the goal of my work is to explain the regulation, cell dynamics and cell organization that is important for the formation of cartilage/bone structures in the head that we all have and, on the other hand, understand the essence of inherited features and being different from each other.
Marketa Kaucka graduated from Molecular Biology and Genetics at Masaryk University in Brno, Czech Republic. She obtained her PhD degree at Masaryk University in a program of Physiology and Immunology and the focus of her PhD work was Wnt/Planar Cell Polarity signaling and impaired cell migration in chronic lymphocytic leukemia. As a part of her PhD program, she spent eight months of professional internship at Karolinska Institutet in the laboratory of Gunnar Schulte. In 2013 Marketa has been awarded EMBO long term fellowship and is currently working as associated research fellow Karolinska Institutet, department of Physiology and Pharmacology and also Molecular Neuroscience.
Nina Kaukua, Degree in Dental Surgery, PhD student
My research is all about dental stem cells. The projects currently focus on Schwann cells residing in sensory nerves and their contribution to pulp cells and hard-matrix producing odontoblasts in the developing and adult tooth as well as during trauma-induced regeneration. I also analyze dental stem cells of the human deciduous and permanent dentition. My results will broaden our knowledge about embryonic and adult dental stem cells including the aspect related to regenerative medicine.
Maryam Khatibi Shahidi, Degree in Dental Surgery, PhD student
After a degree in dental surgery at Karolinska Institutet in 2009, I got accepted as a PhD student in Swedish National Graduate School in Odontological Science. I joined the Adameyko lab in 2012. My projects in Igor Adameyko lab aim mainly towards exploring the role of peripheral nervous system in craniofacial development. Peripheral glial cells have been suggested to have stem cell properties because they are giving rise to melanocytes and endoneural fibroblasts. However, the entire spectrum of plasticity has not been fully elucidated and is of interest for both basic and clinical science. Recently, the role of Schwann cell precursors in development of teeth and parasympathetic ganglia has been the main focus of my studies. These studies revealed an unexpected source of mesenchymal stem cells originating from peripheral nerve that contributes to mouse incisor tooth formation and self-renewal. I master many different basic laboratory techniques and work mainly with preparing, processing, imaging and analyzing tissue samples during different developmental stages. Exploring what is unknown is the main driving force behind my scientific interest. In the future I would like to keep contributing to the research within this field by further dedicating my time and cross-disciplinary knowledge.
Jan Krivanek, Visiting PhD student
I am attending a PhD programme at the Department of Histology and Embryology, Faculty of Medicine in Brno, the Czech Republic. In Igor Adameyko's group I am a visiting student for half a year. What I consider the most exciting about working here at Karolinska Institutet is the opportunity to study the real nature of certain biological processes and their close connection to structural organisation in living organisms using in vivo models. My stay here is dedicated to the study of sensory abilities of teeth in context with their 3D structure. I am trying to elucidate mechanisms that are used for receiving and processing signals coming from outer environment with emphasis on odontoblasts as primary sensory cells. I am trying to use my knowledge acquired from the previous study to do my best here as well as to absorb as much as possible and get theoretical and practical experience that I could use for my future scientific work. I regard my stay here as very motivating for me and thanks to this experience I know more than ever before about which direction in science I want to follow in the future.
All current projects in our laboratory can be divided into three main branches:
- Neurobiology of autonomic nervous system, its ontogeny, evolution and multiple roles in regulating organogenesis and regeneration of innervated organs and tissues.
- Craniofacial development and control of facial shape and skeletogenesis.
- A number of projects related to elaboration of novel cell types and understanding of cellular identity in complex multicellular model systems.
Unexpected origin for important parts of the nervous system. Press release from Karolinska Institutet June 13, 2014
Stem cells from nerves form teeth. Press release from Karolinska Institutet July 28, 2014
Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors.
Science 2014 Jul;345(6192):82-7
Glial origin of mesenchymal stem cells in a tooth model system.
Nature 2014 Sep;513(7519):551-4
Non-canonical functions of the peripheral nerve.
Exp. Cell Res. 2014 Feb;321(1):17-24
Progenitors of the protochordate ocellus as an evolutionary origin of the neural crest.
Evodevo 2013 Apr;4(1):12
Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin.
Cell 2009 Oct;139(2):366-79
Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest.
Development 2012 Jan;139(2):397-410
Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes.
Cell. Mol. Life Sci. 2010 Sep;67(18):3037-55
MYC proteins promote neuronal differentiation by controlling the mode of progenitor cell division.
EMBO Rep. 2014 Apr;15(4):383-91
Murine neural crest stem cells and embryonic stem cell-derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion.
J Tissue Eng Regen Med 2017 01;11(1):129-137
The transcription factor Hmx1 and growth factor receptor activities control sympathetic neurons diversification.
EMBO J. 2013 May;32(11):1613-25
Positional differences of axon growth rates between sensory neurons encoded by Runx3.
EMBO J. 2012 Sep;31(18):3718-29
The retinoic acid inducible Cas-family signaling protein Nedd9 regulates neural crest cell migration by modulating adhesion and actin dynamics.
Neuroscience 2009 Sep;162(4):1106-19
Retrograde signaling onto Ret during motor nerve terminal maturation.
J. Neurosci. 2008 Jan;28(4):963-75
The regulation of Sox9 gene expression by the GATA4/FOG2 transcriptional complex in dominant XX sex reversal mouse models.
Dev. Biol. 2007 Jul;307(2):356-67
Expression and regulation of mouse SERDIN1, a highly conserved cardiac-specific leucine-rich repeat protein.
Dev. Dyn. 2005 Jun;233(2):540-52
Expression and regulation of mouse SERDIN1, a highly conserved cardiac-specific leucine-rich repeat protein.
Dev. Dyn. 2005 Jun;233(2):540-52
Transgenic analysis of Serdin1 expression in mouse.
Adameyko I., Mudry R., Houston-Cummings N., Veselov A., Gregorio C., Tevosian S.
Proceedings of Nizhniy Novgorod State University (in Russian), 8:154-159, 2004.