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OL-protocadherin is essential for growth of striatal axons and thalamocortical projections

Abstract

The ventral telencephalon in the embryonic brain is thought to provide guidance cues for navigation of thalamocortical axons, but the mechanisms involved remain largely elusive. OL-protocadherin (OL-pc), a member of the cadherin superfamily, is highly expressed by striatal neurons in the developing ventral telencephalon. Here we show that OL-pc–deficient (Pcdh10−/−) mice have defects in axon pathways through the ventral telencephalon; for example, thalamocortical and corticothalamic projections cannot cross the ventral telencephalon. In the ventral telencephalon, striatal axons fail to grow out, and, concomitantly, the caudal portion of the globus pallidus and the associated 'corridor' thought to be important for thalamocortical fiber navigation do not form. The inability of the striatum to extend axons is also observed in vitro. These results show that OL-pc is essential for both elongation of striatal axons and patterning of the putative guidance cues for thalamocortical projections.

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Figure 1: Expression of Pcdh10 mRNA in the ventral telencephalon.
Figure 2: Distribution of OL-pc protein and the trajectory of axon fibers in the ventral telencephalon.
Figure 3: Defects of neural pathways in OL-pc–deficient brains.
Figure 4: Defects in putative guidance cues in the caudal part of the ventral telencephalon.
Figure 5: Impaired projection of striatal axons in the OL-pc mutant.
Figure 6: In vitro analysis of striatal axons.
Figure 7: Striatal axon growth in collagen gel cultures.

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Acknowledgements

We thank G. Eguchi for encouragement during the JST PRESTO project. The OL-pc knockout mouse line was generated by Lexicon Pharmaceuticals and maintained by the animal facility in RIKEN CDB with help of H. Miyachi. We thank Y. Suda and S. Aizawa (RIKEN Center for Developmental Biology) for Pax6 and Emx2 mutant mice; Y. Suda for Ebf1, H. Fujisawa (Nagoya University) for Slit1, Slit2 and Neuropilin-2, and M. Tessier-Lavigne (Genentech) for Netrin-1 probe DNAs; T. Terashima, N. Yamamoto and G. Lopez-Bendito for technical guidance; K. Campbell (Cincinnati Children's Hospital Medical Center, University of Cincinnati), N. Osumi (Tohoku University) and S. Itohara (RIKEN Brain Science Institute) for antibodies to Gsh2, Pax6 and Netrin-G1, respectively; E. Aoki and A. Nakayama for the initial phase of the experiments; J.L. Rubenstein, O. Marin and C. Redies for discussion; and H. Ishigami, M. Nomura and C. Yoshii for technical assistance. S.N. is a recipient of a Fellowship of the Japan Society for the Promotion of Science for Junior Scientists. This work was supported by grants (to M.T.) from the program Grants-in-Aid for Specially Promoted Research.

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M.U. conducted experiments and analyzed the mutant mouse data. S.N. analyzed specific phenotypes of the mutant mice. S.T.S. supervised the project in the early phase. M.T. supervised the project and wrote the manuscript. S.H. planned the project and contributed to every aspect.

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Correspondence to Masatoshi Takeichi or Shinji Hirano.

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The authors declare no competing financial interests.

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Uemura, M., Nakao, S., Suzuki, S. et al. OL-protocadherin is essential for growth of striatal axons and thalamocortical projections. Nat Neurosci 10, 1151–1159 (2007). https://doi.org/10.1038/nn1960

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