The Human brain consists of over 100 billion neurons. The main function of neurons is to integrate the information input from the neighboring cells and to transmit the output signal to connected neurons. Therefore, these cells have specialized morphology with highly elaborated dendritic processes allowing to receive signals and axons that transmit impulses to the target cells. Proper formation and organization of neuronal dendritic fields is important for the establishment of functional neuronal circuits and brain functioning.
The number of dendrites and their branching pattern correlates with the function of particular type of neuron and connections it receives. Thus, the diversity of dendritic arbor morphology in the nervous system is necessary to fulfill a wide range of specific computational needs and out to be precisely regulated.
Studies conducted at the Nencki Institute of Experimental Biology dissected the novel molecular pathway underlying the patterning and growth of dendritic arbors. “Since abnormalities in dendritic tree arborization and growth are often reported to cause learning and memory impairments and are known to be associated with numerous neurological disorders like schizophrenia or autism spectrum disorders, it is of great interest to understand the processes that govern dendritic patterning” – says prof. dr. hab. Tomasz Prószyński.
In the recent study performed in the Laboratory of Synaptogenesis led by dr. hab. Tomasz Prószyński the researches unraveled new molecular players critical for proper development of dendritic arbors. The results of the study were published in the prestigious PLOS Biology journal – KO. Rojek, J. Krzemień, H. Doleżyczek, P. Boguszewski, L. Kaczmarek, W. Konopka, M. Rylski, J. Jaworski, L. Holmgren, and TJ. Prószyński (2019); “Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice” (https://doi.org/10.1371/journal.pbio.3000253). The journal aims to cover the most important aspects of biology and make it accessible to broad audience. The project was founded by the grants awarded by National Science Centre and published in collaboration with our colleagues from International Institute of Molecular and Cell Biology in Warsaw, Center for Postgraduate Medical Education, and Karolinska Institute in Stockholm.
In the study the authors proposed that two genes, Amot and Yap1, usually engaged in processes related to tissue growth, homeostasis and tumorigenesis are critical for proper brain development and dendritic arbors growth and patterning. That was a great scientific journey – say Katarzyna Rojek and Joanna Krzemień, two young researches who conceptualized and conducted the study. In our experiments we used genetically modified animals that did not express Amot or Yap1 specifically in neuronal cells. Mice lacking Amot or Yap1 had impaired dendritic tree morphology of Purkinje cells in cerebellum and altered cerebellar architecture. Cerebellum plays a critical role in balance and locomotor coordination maintenance. Consistently, we noticed that our mutant animals had severe impairments in locomotor coordination. When placed on the rotating rod they had problems with maintaining their balance. An automatic computer-based analysis of their walking cycle also showed that mutant mice have impairments in paw coordination when walking. Authors additionally documented that Amot and Yap1 function through the regulation of S6 kinase (S6K) which regulates phosphorylation of S6 protein that controls protein translation in cells. “This was quite unexpected observation, since Yap1 usually regulates transcription of selected genes” – says Katarzyna Rojek.
Interestingly, Amot and Yap1 have been recently implicated in human brain disorders, such as autism spectrum disorder, Alzheimer disease, and dementia. “It would be of great interest to continue our research on Amot and Yap1 and investigate pharmacological relevance of our discovery. We hope that in the future, a better understanding of the molecular processes underlying dendritic tree patterning could help to develop new treatment modalities for various neurological and psychiatric conditions” – says professor dr. hab. Tomasz Prószyński.
dr. hab. Tomasz Prószyński
Nencki Institute of Experimental Biology
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