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Monoallelic yet combinatorial expression of variable exons of the protocadherin-α gene cluster in single neurons

Abstract

Diverse protocadherin-α genes (Pcdha, also called cadherin-related neuronal receptor or CNR) are expressed in the vertebrate brain. Their genomic organization involves multiple variable exons and a set of constant exons, similar to the immunoglobulin (Ig) and T-cell receptor (TCR) genes. This diversity can be used to distinguish neurons. Using polymorphisms that distinguish the C57BL/6 and MSM mouse strains, we analyzed the allelic expression of the Pcdha gene cluster in individual neurons. Single-cell analysis of Purkinje cells using multiple RT-PCR reactions showed the monoallelic and combinatorial expression of each variable exon in the Pcdha genes. This report is the first description to our knowledge of the allelic expression of a diversified receptor family in the central nervous system. The allelic and combinatorial expression of distinct variable exons of the Pcdha genes is a potential mechanism for specifying neuron identity in the brain.

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Figure 1: Strategy for obtaining the expression profiles of Pcdha transcripts in individual cells.
Figure 2: Expression of Pcdha mRNA in the cerebellum of P21 mice.
Figure 3: Split single-cell RT-PCR strategy for Purkinje cells.
Figure 4: Model of the monoallelic and combinatorial expression of the variable exons of Pcdha in single cells.

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Acknowledgements

We thank T. Yamamori for suggestions and the use of his laboratory, H. Yamane for producing the design of Figure 1b, T. Shiroishi for providing MSM strains and members of the laboratory of T.Y. for suggestions and discussion during the course of this work. This work was supported by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (T.Y.), the Uehara Memorial Foundation, the Takeda Foundation and CREST (Core Research for Evolutional Science and Technology) of JST (Japan Science and Technology Agency).

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Correspondence to Takeshi Yagi.

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Supplementary information

Supplementary Fig. 1

Sequences of CNR/Pcdhα isoforms from the region amplified by RT-PCR. (PDF 611 kb)

Supplementary Fig. 2

Biallelic expression of β-actin transcripts from single Purkinje cells. (PDF 893 kb)

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Esumi, S., Kakazu, N., Taguchi, Y. et al. Monoallelic yet combinatorial expression of variable exons of the protocadherin-α gene cluster in single neurons. Nat Genet 37, 171–176 (2005). https://doi.org/10.1038/ng1500

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