Tyro3 in myelin damage and repair
We have previously established that the loss of Tyro3 results in changes to the ultrastructure of myelin, including a reduction in the thickness of myelin surrounding nerves, as well as changes at the regions known as paranodes, where myelin attaches to the nerves. However, the functional outcomes of these changes remains unclear.
This project will further explore the role of Tyro3 during developmental myelination and remyelination following myelin damage, using a mouse strain in which the Tyro3 gene has been deleted. In particular, this project will assess the behavioural changes resulting from loss of Tyro3 following myelin damage. In addition, the cellular mechanism underlying the role of Tyro3 in myelination will be investigated using mice in which Tyro3 has been specifically deleted from neurons or oligodendrocytes.
Figure 1: Tyro3 deficiency is associated with disruptions to paranodal structure.
Blades, F., Chambers, J.D, Aumann, T.D., Nguyen, C.T.O., Wong, V.H.Y., Aprico, A., Nwoke, E.C., Bui, B.V, Grayden, D.B., Kilpatrick, T.J and Binder, M.D. (2022) White matter tract conductivity is resistant to wide variations in paranodal structure and myelin thickness accompanying the loss of Tyro3: An experimental and simulated analysis. Brain Structure and Function 227:2035-2048.
Blades, F., Wong, V.H., Nguyen, C.T.O., Bui, B.V., Kilpatrick, T.J. and Binder, M.D. (2020) Tyro3 contributes to retinal ganglion cell function, survival and dendritic density in the mouse retina. Front. Neurosci. 14:840
Blades, F., Aprico, A. Akkermann, R., Ellis, S., Binder, M.D*. and Kilpatrick, T.J.* (2018) The TAM receptor Tyro3 is a critical regulator of myelin thickness in the central nervous system. Glia 1-12
Akkermann, R., Aprico, A., Perera, A.A., Bujalka, H., Cole A.E., Xiao, J., Field, J., Kilpatrick, T.J., and Binder, M.D. (2017) The TAM Receptor Tyro3 regulates myelination in the central nervous system. Glia 65:581-591