In 2016, the research team of Professor Niovi Sandama at the Department of Biological Sciences of the University of Cyprus described KATNAL2 as a "cellular samurai" that divides the microtubules of the cytoskeleton into fundamental cellular processes such as cell division and sensory cellular eyelashes. KATNAL2 concentrates on international interest after associating its mutations as high risk agents for sporadic autism in large patient genomic sequencing studies. In a new recent study, coordinated by the University of Cyprus and colleagues at the University of California (UC Berkeley and UC San Francisco), an attempt was made to understand the involvement of KATNAL2 in the molecular mechanisms of pathogenesis in autism. With this goal, the researchers monitored the embryonic development of the Xenopus tropicalis frog, an organization that has been used as a valuable model for the development of vertebrates, following the application of the most recent genome modification methodology (CRISPR / Cas9 genome editing). The findings were recorded in a recent publication (15 October 2018) in the international scientific journal Developmental Biology (Elsevier) *.
Serious problems can be caused by the absence of KATNAL2 protein in the development of the nervous system, organogenesis and organization of sensory and cervical epithelial embryogenesis.
Researchers have shown that in the developing embryo the KATNAL2 protein is enriched in the nervous system (especially in the area of the moles of the moose) and in organs and tissues that have sensory or crural epithelia such as the epidermis, ears, eyes, kidneys, pharynx and lungs. The absence of KATNAL2, due to targeted gene modification, causes serious neurogenic problems by inhibiting neural tube neuronal smoothing and migration of neural crest cells. The most dramatic effect of the absence of KATNAL2 on the development of the nervous system is the reduction in the size of the teleness, accompanied by drastically reduced number of progenitor nerve cells of the ventricular zone progenitor cells. Organogenesis in general is also problematic by shortening the sagittal shaft, decreasing cranial cartilage and eye size and staining. Modified frog embryos often had oedema due to renal failure. Sensory eyelashes and cervical epithelia in various organs and tissues were defoliated, with incorrect organization and with an irregular orientation of the sub-acute actin network.
Overall, the findings highlight the contribution of KATNAL2 protein to signalling pathways associated with the establishment of cellular orientation in the growth model architecture, which is critical for the formation of the nervous system and also for organogenesis in general. As it is now accepted that autism is a disturbance of the proper development of the nervous system during embryogenesis, deepening the understanding of the abnormalities in the mechanisms involved is valuable for elucidating the pathology of this neurodevelopmental disease at a molecular level.
The research program was funded by the University of Cyprus and the University of California. A popularized summary of the scientific article is hosted on the Atlas of Science website (http://atlasofscience.org/how-a-cellular-samurai-may-belinked-to-autism/), a forum that highlights new articles from international literature aimed at diffusion to international media.
*Publication
Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos. Willsey HR, Walentek P, Exner CRT, Xu Y, Lane AB, Harland RM, Heald R, Santama N.