Dev cell: how neuronal mutations disrupt brain connectivity

December 18, 2019 news / BIOON / -- axons are long linear extensions of neurons that can send electrical signals to other brain cells Because of the axon connections, our brain and body can do all the necessary tasks Before we were born, axons had grown throughout the gray matter area and connected properly as the brain developed Recently, researchers at UNC medical school have discovered the cause of rare neurodevelopmental abnormalities due to faulty connections (image source: www Pixabay Com) Dr EVA Anton, Professor of cell biology and physiology at UNC Chapel Hill, published in the Journal of developmental cell, showed how two gene mutations alter the function of nerve cilia, leading to the rare Joubert syndrome related disease (JSRD) "Our experiments show that ciliary signal transduction promotes axon bundle development and connection, and destruction of ciliary signal can lead to axon deformity in JSRD," Anton said Although cilia have been found in most cell types, their importance in brain development has not been fully recognized until recently Now scientists know that cilia sense the environment around them, and that dysfunctional cilia disrupt axon growth and connectivity during fetal development Infants with ciliary dysfunction and associated irregular axon growth and connectivity will have JSRD People with this disease experience stunting, mental retardation, abnormal respiratory rhythm, difficulty in controlling physical movements, and other serious health problems But it is not clear how these symptoms occurred Anton and colleagues used a mouse model carrying mutations in the arl13b and inpp5 genes (mutations associated with JSRD patients) to study the effects of ciliary dysfunction on axonal connectivity and brain development using photogenetic methods In mice, they found that mutations in arl13b or inpp5e weakened the ability of cilia to act as a signaling hub Furthermore, Anton and his colleague discovery protein pi3kakt activity changes, thus regulating axon behavior "By revealing the importance of primary cilia in the emergence of brain connectivity, it helps us understand how ciliary disorders lead to axonal defects in JSRD related diseases," Anton said Sources of information: scientists show how tiny, mutated neuron antenna impair brain connectivity original sources: Jiami Guo, James M Otis, Sarah K suciu, Christy Catalano, Lei Xing, sandii constable, Dagmar wachten, Stephanie Gupton, Janice Lee, Amelia Lee, Katherine H Blackley, Travis Ptacek, Jeremy M Simon, Stephane schurmans, garret D stub, Tamara Caspary, E.S Anton Primary Cilia Signaling Promotes Axonal Tract Development and Is Disrupted in Joubert Syndrome-Related Disorders Models Developmental Cell , 2019; 51 (6): 759 DOI: 10.1016/j.devcel.2019.11.005