Our lab studies the role of polysialic acid in regulating the nervous system and the use of polysialic acid to promote tissue repair.
Vertebrates have evolved a unique mechanism for regulation of cell interactions in order to accommodate the molecular and functional complexity of the central nervous system. This mechanism utilizes a very large and abundant cell surface carbohydrate (polysialic acid or PSA, specifically attached to the neural cell adhesion molecule NCAM) to titrate the intimacy of membrane-membrane contacts. By interfering with membrane apposition, PSA expression is able to cause a global reduction in cell interactions and thereby create permissive conditions for changes in cell position and shape. During development of the nervous system, these permissive conditions are known to facilitate the migration of neuronal precursors, the guidance of axons to their targets, and the formation of appropriate synapses.
Recently our lab has focused on the retention of PSA in certain regions of the brain known to exhibit physiological and/or structural plasticity. While the role of PSA in the adult brain is similar at the cellular level to that during development, the physiological context is of course very different. Those contexts have led to a series of projects in the lab dealing with:
El Maarouf A, Moyo-Lee Yaw and Rutishauser U. 2014 Improved Stem Cell-Derived Motoneuron Survival, Migration, Sprouting and Innervation with Enhanced Expression of Polysialic Acid. Cell Transplantation 2014, Mar 3.
Battista D, Ganat Y, El Maarouf A, Studer L and Rutishauser U. 2014 Enhancement of polysialic acid expression improves function of ES-derived dopamine neuron grafts in Parkinsonian mice. Stem Cells Translational Medicine 2014; 3(1): 108-113.
Mousumi Ghosh, Luis M. Tuesta, Rocio Puentes, Samik Patel, Kiara Melendez, Abderrahman El Maarouf, Urs Rutishauser, Damien D. Pearse. 2012 PST-expressing Schwann cells readily migrate, support corticospinal axon regeneration and promote functional restitution after implantation into the contused spinal cord , Glia. 2012; 60(6):979-92.
Yosif M. Ganat, Sonja Kriks, Elizabeth L. Calder, Edmund Y. Tu , Fan Jia, Neil Harrison, Mark J. Tomishima, Urs Rutishauser and Lorenz Studer. 2012 BAC transgenic ESC reporter line analysis identifies midbrain dopaminergic neuron stages suitable for efficient in vivo engraftment and in vitro gene discovery J Clin Invest. Aug 1;122(8):2928-39. Epub 2012 Jul.
Battista D, Rutishauser U. (2010) Removal of polysialic acid triggers dispersion of subventricularly derived neuroblasts into surrounding CNS tissues. J Neurosci. 30(11):3995-4003.