Important Discoveries in Relation to the Development of the Spleen

The results of the research of scientists from the Veterinary Faculty of the University of Ljubljana are important not only for understanding normal spleen development but for understanding the emergence of inborn disturbances in its development.

Authors: Gregor Majdič, Katja Kozinc


Researchers from the Veterinary Faculty of the University of Ljubljana Katja Kozinc and Gregor Majdič and their Italian colleagues researched molecular mechanisms of the development of the spleen and disturbances that lead to human diseases, which are still largely unknown. They primarily assessed the impact of the TLX1 gene in spleen development.  

The results showed that TLX1 regulates the development of the spleen through modulation of retinoic acid signalling pathway. The mice model showed that the absence of TLX1 transcription factor resulted in disturbances in the development of the spleen in mice due to interference of the retinoic acid signalling pathways. The interrupted expression of the retinoic acid was reflected in early maturing of mesenchymal cells in the spleen, which was followed by reduced formation of blood vessels and consequently to significantly reduced spleen size. It was also determined that the SF-1 gene acts as the major regulator of spleen development, since it regulated the expression of the TLX1 gene and some other genes which are important for spleen development. The results indicated the molecular route for spleen development, which starts with the SF-1 gene, then triggers the expression of the TLX1 gene, then inhibits the retinoic acid signalling pathways, finally ensuring normal spleen development. The research results are important not only for understanding normal spleen development but for the understanding of molecular mechanisms of foetal spleen development and to help with the future development of treatment methods for such pathologies.

The achievement was published in the Journal of Clinical Investigation, with impact factor of 12,755, which is placed on third position among 124 journals in the field of Experimental medicine in Web of Science database. 

Source: J Clin Invest. 2016 Jul 1;126(7):2452-64. doi: 10.1172/JCI82956. Epub 2016 May 23. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development. Prepisovalni dejavnik Tlx1 z nadzorom nad sporočilno potjo retinojske kisline ureja pravilen razvoj vranice Lenti E, Farinello D, Yokoyama KK, Penkov D, Castagnaro L, Lavorgna G, Wuputra K, Sandell LL, Tjaden NE, Bernassola F, Caridi N, De Antoni A, Wagner M, Kozinc K, Niederreither K, Blasi F, Pasini D, Majdic G, Tonon G, Trainor PA, Brendolan A.