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December 14, 2007

Guided nerves in the embryonic brain

Japanese biologists identify a protein critical to the normal development of the embryonic brain

Figure 1: (a) Nerve fibers are misrouted in various ways in the brain of a mutant mouse deficient in the protein OL-protocadherin. (b) In a normal mouse brain, nerve fibers grow towards the cortex. (The slices of brain tissue were labeled with DiI).

© Nature Neuroscience/Nature Publishing Group/10/1154 (2007)

Early in embryonic development, nerves grow and spread through the brain. If the nerves grow in the wrong direction or are stunted, it is fatal to the embryo. Growing nerve fibers appear to be guided by an invisible cue to travel along specific pathways making the decision to change direction or branch out at particular points.

This specific directional growth of embryonic nerve fibers has been the focus of a study recently published in Nature Neuroscience1. Japanese biologists have demonstrated that a protein called OL-protocadherin (OL-pc) is crucial to the correct growth of particular nerves in the developing brain.

The team, led by Shinji Hirano and Masatoshi Takeichi of the RIKEN Center for Developmental Biology, Kobe, developed a population of mice that lack the gene for OL-pc and therefore don’t produce the protein. The team was able to show that, in these mutant mice, particular nerve fibers grew in a disorganized manner or were stunted and the embryos died within weeks. In normal mice, comparable nerve fibers grew in an orderly fashion (Fig. 1). Stained sections of brain tissue showed that the presence of OL-pc matched the regions of nerve growth. The protein was found both along the nerve fibers and at their growing tips.

Hirano and colleagues found OL-pc most abundantly in the small striatal region of the forebrain. This is the major input station of nerves associated with bodily movement. The group showed that striatal fragments transplanted outside their normal area extended nerve fibers in the normal orientation, suggesting the existence of a guidance mechanism. Also, if these striatal nerve fibers did not grow properly, the team found that non-striatal nerves travelling to other parts of the brain became tangled or misrouted, suggesting that other nerves require normal striatal nerve extension for their progression.

OL-pc molecules tend to stick to each other and so interaction between them along nerve fibers may give rise to a signal that guides growth. Alternatively, OL-pc may act as a receptor for an, as yet, unknown cue.

Although the results suggest that OL-pc is important for the growth of striatal nerve fibers, other mechanisms seem to coexist for ensuring the correct migration of these nerves. The cooperative mechanisms between these mechanisms need to be determined in the future. Further study of importance of striatal nerve fibers in guiding nerves to other brain areas and the unveiling of the signaling mechanism of OL-pc are next, says Hirano.

References

  1. Uemura, M., Nakao, S., Suzuki, S.T., Takeichi, M. & Hirano, S. OL-protocadherin is essential for growth of striatal axons and thalamocortical projections. Nature Neuroscience 10, 1151–1159 (2007). |  | (Link)