Experimental and molecular development of lympho-myeloid organs
The project focuses on the organogenesis of hemopoietic organs, more specifically on the formation of the microenvironment involved in the differentiation of hemopoietic cells, the network of cellular and extracellular elements and its molecular regulation. We specifically concentrate on two stages in the organogenesis of myeloid and lymphoid organs; 1) the emergence of the organ rudiment during gastrulation; and 2) the histogenesis of the organ-specific microenvironment, during which the ‘niche’ becomes competent to receive and ‘nurture’ hemopoietic cells. In our experiments, we combine classical embryomanipulation techniques (embryonic chimera technique, ablation, implantation, parabiosis, transplantation, in vitro recombinant tissue culture, immunocytochemistry, in situ hybridization) with different developmental biology methods. Deep understanding of the microenvironment of lympho-myeloid organs and the in vitro modelling based on this knowledge is of both theoretical and, in the long term, of practical importance.
Highlighted research topics:
- Molecular interactions in lymphoid organ morphogenesis: effects of homeobox genes and chemokines (C-X-C chemokine ligand 12 (CXCL12) and CXCL13) on bursa of Fabricius or spleen development and colonization by hemopoietic cells.
- Development of primary lymphoid organs: in our experiments, we combine classical embryomanipulation techniques (chimerization, ablation, implantation, parabiosis, transplantation, in vitro recombinant tissue culture, immunocytochemistry, in situ hybridization) with gene manipulation (retroviral gene delivery). We study the effects of BMP, VEGF, SHH, WNT and CXCL12 growth factors and chemokines on the developing primary lymphoid organs (thymus, bursa of Fabricius, bone marrow).
- Ontogenesis of neuronal tissue-associated macrophages: we study the lineage mapping of MHCII-positive cells of mesodermal and/or haemopoietic origin in the peripheral and central nervous system. Manipulation of CSF1R receptor transgenic (MacRed) embryos and CX3CR1-GFP mice allows embryonic and adult characterization of microglia-like cells.
- Role of the chorda dorsalis in lymphomyeloid organ development