MDC Researchers Gain New Insights into the Process of Axon Myelination

Dr. Tamara Grigoryan from the research group of Professor Walter Birchmeier at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch has gained new insights into the formation and differentiation of axons, through which nerve cells receive or transmit information. Axons can be myelinated (wrapped in a myelin sheath) – allowing for faster nerve impulse conduction – or non-myelinated (without a myelin sheath). In collaboration with the research group of Professor Carmen Birchmeier, developmental biologist at the MDC, Dr. Grigoryan showed in mice how axon myelination or non-myelination is regulated in the peripheral nervous system (PNAS, doi: /10.1073/pnas.1310490110)*.

Besides neurons, glial cells are also key players in the nervous system. “Without the support of the glial cells, the nerve cells would not be able to function,” said Dr. Grigoryan. In the peripheral nervous system the Schwann cells play an important role. These are a group of glial cells named after their discoverer Theodor Schwann (1810-1882). Schwann cells surround the axons and form a myelin sheath. “Following a nerve injury in the peripheral nervous system, the Schwann cells trigger axon regeneration.” However, not all axons have a myelin sheath. How is this process regulated?

“At the beginning of their development in the embryo, the axons are grouped in bundles as extension of a nerve cell and are surrounded by a Schwann cell,” said Dr. Grigoryan. “At birth, however, the Schwann cell begins to sort out the thick axons from the bundle and to wrap them in a myelin sheath. The thin axons are not sorted out – they remain bundled and do not receive a myelin sheath. Researchers call this process axonal radial sorting.”

The large and thicker axons are wrapped by the Schwann cells in multiple layers. Due to this myelin insulation – like a power cable sheathed in plastic – these axons, for example of motor neurons, can transfer information very fast. This is why you can pull your hand quickly away from a hot stove, because the axons signal the information “hot – danger of burns”.

This fundamental process is regulated by a signaling pathway which researchers in Professor Walter Birchmeier’s laboratory have been studying for many years – the Wnt/beta-catenin signaling pathway. It is one of the best-studied signaling pathways. It plays a key role in embryonic development, cell growth (proliferation), cell maturation or cell specialization (differentiation) and in the regulation of stem cells, and, as the most recent work from the MDC now shows, even in the formation and differentiation of axons.

The research team attaches special significance to its discovery, since a dysregulation of Schwann cells can lead to a number of serious diseases. Dr. Grigoryan and her colleagues hope that this discovery will not only contribute to a better understanding of Schwann cell development but also to deeper insight into the pathogenesis of diseases in which these cells are involved.

*Wnt/Rspondin/?-catenin signals control axonal sorting and lineage progression in Schwann cell development

Tamara Grigoryana, Simone Steina, Jingjing Qia, Hagen Wendeb, Alistair N. Garrattc, Klaus-Armin Naved, Carmen Birchmeierb, and Walter Birchmeiera,1

aCancer Research Program and bNeuroscience Program, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; cCenter for Anatomy, Charite? University Hospital, 10117 Berlin, Germany; and dDepartment of Neurogenetics, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany

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