Immunolocalization of Ephexin-1 in the Developing Canine Cerebellum


Ephexin-1 functions as guanine nucleotide exchange factors for the Rho-type GTPases which have important roles in neuronal development including axon guidance, migration, morphogenesis, and plasticity of neurons. As little is known about ephexin-1 in the cerebellum, we investigated the immunolocalization of ephexin-1 in the developing canine cerebellum. While the cellular maturation was followed by the temporal pattern, the calbindin D-28k and ephexin-1 immunoreactivities gradually increased in developing canine cerebellum. When compared to the calbindin D-28k immunoreactivities, belated ephexin-1 immunolocalization was observed in the Purkinje cells which aligned a single layer during cerebellar development. These results suggest that ephexin-1 might play an important role in the development of the Purkinje cells during the first two postnatal weeks based on its immunolocalization in the present study.

Share and Cite:

Park, H. , Chang, I. , Kim, H. and Yoon, S. (2014) Immunolocalization of Ephexin-1 in the Developing Canine Cerebellum. Neuroscience and Medicine, 5, 9-14. doi: 10.4236/nm.2014.51002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Roger, J.H. (1989) Immunoreactivity for Calretinin and Other Calcium-Binding Proteins in Cerebellum. Neuroscience, 31, 711-721.
[2] Fortin, M., Marchand, R. and Parent, A. (1998) Calcium-Binding Proteins in Primate Cerebellum. Neuroscience Research, 30, 155-168.
[3] Siso, S., Tort, S., Aparici, C., Perez, L., Vidal, E. and Pumarola, M. (2003) Abnormal Neuronal Expression of the Calcium-Binding Proteins, Parvalbumin and Calbindin D-28k, in Aged Dogs. Journal of Comparative Pathology, 128, 9-14.
[4] Celio, M.R. (1990) Calbindin D-28k and Parvalbumin in the Rat Nervous System. Neuroscience, 35, 375-475.
[5] Bastianelli, E. (2003) Distribution of Calcium-Binding Proteins in the Cerebellum. Cerebellum, 2, 242-262.
[6] Yoon, S.P., Chung, Y.Y., Chang, I.Y., Kim, J.J., Moon, J.S. and Kim, H.S. (2002) Postnatal Development of Calbindin D-28k and Parvalbumin Immunoreactivities in the Canine Hippocampus. Journal of Chemical Neuroanatomy, 19, 143-154.
[7] Moon, J.S., Kim, J.J., Chang, I.Y., Chung, Y.Y., Jun, J.Y., You, H.J. and Yoon, S.P. (2002) Postnatal Development of Calbindin D-28k and Parvalbumin Immunoreactivities in the Canine Anterior Cingulated Cortex: Transient Expression in Layer V Pyramidal Cells. International Journal of Developmental Neuroscience, 20, 511-519.
[8] Phemister, R.D. and Young, S. (1968) The Postnatal Development of the Canine Cerebellar Cortex. Journal of Comparative Neurology, 134, 243-253.
[9] Ayala, R., Shu, T. and Tsai, L.H. (2007) Trekking across the Brain: The Journey of Neuronal Migration. Cell, 128, 29-43.
[10] Peng, Y.J., He, W.Q., Tang, J., Tao, T., Chen, C., Gao, Y.Q., Zhang, W.C., He, X.Y., Dai, Y.Y., Zhu, N.C., Lv, N., Zhang, C.H., Qiao, Y.N., Zhao, L.P., Gao, X. and Zhu, M.S. (2010) Trio Is a Key Guanine Nucleotide Exchange Factor Coordinating Regulation of the Migration and Morphogenesis of Granule Cells in the Developing Cerebellum. The Journal of Biological Chemistry, 285, 24834-24844.
[11] Rodrigues, N.R., Theodosiou, A.M., Nesbit, M.A., Campbell, L., Tandle, A.T., Saranath, D. and Davies, K.E. (2000) Characterization of Ngef, a Novel Member of Dbl Family of Genes Expressed Predominantly in the Caudate Nucleus. Genomics, 65, 53-61.
[12] Jaffe, A.B. and Hall, A. (2005) Rho GTPases: Biochemistry and Biology. Annual Review of Cell and Developmental Biology, 21, 247-269.
[13] Luo, L. (2000) Rho GTPases in Neuronal Morphogenesis. Nature Reviews. Neuroscience, 1, 173-180.
[14] Wong, K., Ren, X.R., Huang, Y.Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S.M., Mei, L., Wu, J.Y., Xiong, W.C. and Rao, Y. (2001) Signal Transduction in Neuronal Migration: Roles of GTPase Activating Proteins and the Small GTPase Cdc42 in the Slit-Robo Pathway. Cell, 107, 209-221.
[15] Klein, R. (2004) Eph/Ephrin Signaling in Morphogenesis, Neural Development and Plasticity. Current Opinion in Cell Biololgy, 16, 580-589.
[16] Govek, E.E., Newey, S.E. and Van Aelst, L. (2005) The Role of the Rho GTPases in Neuronal Development. Genes & Development, 19, 1-49.
[17] Murai, K.K. and Pasquale, E.B. (2005) New Exchanges in Eph-Dependent Growth Cone Dynamics. Neuron, 46, 161-163.
[18] Shi, L., Fu, A.K. and Ip, N.Y. (2010) Multiple Roles of the Rho GEF Ephexin1 in Synapse Remodeling. Communicative & Integrative Biology, 3, 622-624.
[19] Chang, I.Y., Ohn, T., Ko, G.S., Yoon, Y., Kim, J.W. and Yoon, S.P. (2012) Immunolocalization of Steroidogenic Acute Regulatory Protein-Related Lipid Transfer (START) Domain-Containing Proteins in the Developing Cerebellum of Normal and Hypothyroid Rats. Journal of Chemical Neuroanatomy, 43, 28-33.
[20] Tolbert, D.L. and Clark, B.R. (2000) Olivocerebellar Projections Modify Hereditary Purkinje Cell Degeneration. Neuroscience, 101, 417-433.
[21] Simat, M., Ambrosetti, L., Lardi-Studler, B. and Fritschy, J.M. (2007) GABAergic Synaptogenesis Marks the Onset of Differentiation of Basket and Stellate Cells in Mouse Cerebellum. The European Journal of Neuroscience, 26, 2239-2256.
[22] Haag, N., Schwintzer, L., Ahuja, R., Koch, N., Grimm, J., Heuer, H., Qualmann, B. and Kessels, M.M. (2012) The Actin Nucleator Cobl Is Crucial for Purkinje Cell Development and Works in Close Conjunction with the F-Actin Binding Protein Abp1. The Journal of Neuroscience, 32, 17842-17856.
[23] Oostland, M. and van Hooft, J.A. (2013) The Role of Serotonin in Cerebellar Development. Neuroscience, 248C, 201-212.
[24] Schmucker, D. and Zipursky, S.L. (2001) Signaling Downstream of Eph Receptors and Ephrin Ligands. Cell, 105, 701-704.
[25] Rosas, O.R., Figueroa, J.D., Torrado, A.I., Rivera, M., Santiago, J.M., Konig-Toro, F. and Miranda, J.D. (2011) Expression and Activation of Ephexin Is Altered after Spinal Cord Injury. Developmental Neurobiology, 71, 595-607.

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.