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Localization of the type 1 corticotropin releasing factor receptor (CRF-R1) in the embryonic mouse cerebellum

  • Published:
Journal of Neurocytology

Abstract

Corticotropin releasing factor (CRF) is present in the adult, as well as in the embryonic and postnatal rodent cerebellum. Further, the distribution of the type 1 CRF receptor has been described in adult and postnatal animals. The focus of the present study is to determine the distribution and cellular relationships of the type 1 CRF receptor (CRF-R1) during embryonic development of the cerebellum. Between embryonic day (E)11 and E12, CRF-R1 immunoreactive puncta are uniformly distributed in the ventricular zone, the site of origin of Purkinje cells, nuclear neurons, and GABAergic interneurons, as well as the germinal trigone, the birthplace of the precursors of granule cells. Between E13 and 18, the distribution of immunolabeled puncta decreases in both the ventricular zone and the germinal trigone and increases in the intermediate zone, as well as in the dorsal aspect of the cerebellar plate. Between E14 and 18, antibodies that label specific populations of cerebellar neurons were combined with the antibody for the receptor to determine the cellular elements that expressed CRF-R1. At E14, CRF-R1 immunoreactivity is co-localized in neurons immunolabeled with PAX-2, an antibody that is specific for GABAergic interneurons. These neurons continue to express CRF-R1 as they migrate dorsally toward the cerebellar surface. Between E16 and 18, Purkinje cells, immunolabeled with calbindin, near the dorsal surface of the cerebellum express CRF-R1 in their cell bodies and apical processes. CRF has been shown to have a depolarizing effect on adult and postnatal Purkinje cells. Further, CRF has been shown to contribute to excitability of hippocampal neurons during embryonic development by binding to CRF-R1; depolarization induced excitability appears to be critical for cell survival. The location of the type one CRF receptor and the presence of its primary ligand, CRF, in the germinal zones of the cerebellum and in migrating neurons suggest that this receptor/ligand interaction could be important in the regulation of neuronal survival through cellular mechanisms that lead to depolarization of embryonic cerebellar neurons.

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References

  • ALTMAN, J. (1972) Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer. J. Comp. Neurol. 145, 353–398.

    PubMed  Google Scholar 

  • ALTMAN, J. & BAYER, S. (1978) Prenatal development of the cerebellar system in the rat. II. Cytogenesis and histogenesis of the inferior olive, pontine gray, and the precerebellar reticular nuclei. Journal of Comparative Neurology 179, 49–76.

    PubMed  Google Scholar 

  • ALTMAN, J. & BAYER, S. (1997) Development of the Cerebellar System in Relation to its Evolution, Structure, and Functions. New York: CRC Press.

    Google Scholar 

  • ALTMAN, J. & BAYER, S. A. (1978) Prenatal development of the cerebellar system in rat. I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum. J. Comp. Neurol. 178, 23–48.

    Google Scholar 

  • BARAM, T. Z. & HATALSKI, C. G. (1998) Neuropeptidemediated excitability: A key triggering mechanism for seizure generation in the developing brain. Trends Neurosci 21, 471–476.

    PubMed  Google Scholar 

  • BEHAN, D. P., GRIGORIADIS, D. E., LOVENBERG, T. W., CHALMERS, D. T., HEINRICHS, S., LIAW, C. W. & DE SOUZA, E. B. (1996) Neurobiology of corticotropin releasing factor (CRF) receptors and CRFbinding protein: Implications for the treatment of CNS disorders. Mol. Psychiatry 1, 265–277.

    PubMed  Google Scholar 

  • BISHOP, G. A. (1990) Neuromodulatory effects of corticotropin releasing factor on cerebellar Purkinje cells: An in vivo study in the cat. Neuroscience 39, 251–257.

    PubMed  Google Scholar 

  • BISHOP, G. A. (2002) Development of a corticotropin releasing factor-mediated effect on the firing rate of Purkinje cells in the postnatal mouse cerebellum. Exp. Neurol. 178, 165–174.

    PubMed  Google Scholar 

  • BISHOP, G. A. & KING, J. S. (1992) Differential modulation of Purkinje cell activity by enkephalin and corticotropin releasing factor. Neuropeptides 22, 167–174.

    PubMed  Google Scholar 

  • BISHOP, G. A. & KING, J. S. (1999) Corticotropin releasing factor in the embryonic mouse cerebellum. Exp. Neurol. 160, 489–499.

    PubMed  Google Scholar 

  • BISHOP, G. A., SEELANDT, C. M. & KING, J. S. (2000) Cellular localization of corticotropin releasing factor receptors in the adult mouse cerebellum. Neuroscience 101, 1083–1092.

    PubMed  Google Scholar 

  • BITTENCOURT, J. C. & SAWCHENKO, P. E. (2000) Do centrally administered neuropeptides access cognate receptors? An analysis in the central corticotropinreleasing factor system. J. Neurosci. 20, 1142–1156.

    PubMed  Google Scholar 

  • CHALMERS, D. T., LOVENBERG, T. W., GRIGORIADIS, D. E., BEHAN, D. P. & DESOUZA, E. B. (1996) Corticotropin-releasing factor receptors: From molecular biology to drug design. TIPS 17, 166–172.

    PubMed  Google Scholar 

  • CHEDOTAL, A. & SOTELO, C. (1992) Early development of olivocerebellar projections in the fetal rat using CGRP immunocytochemistry. European Journal of Neuroscience 4, 1159–1179.

    PubMed  Google Scholar 

  • CHEDOTAL, A. & SOTELO, C. (1993) The ‘creeper stage’ in cerebellar climbing fiber synaptogenesis precedes the ‘pericellular nest'—Ultrastructural evidence with parvalbumin immunocytochemistry. Developmental Brain Research 76, 207–220.

    PubMed  Google Scholar 

  • CHEN, Y., BRUNSON, K. L., MULLER, M. B., CARIAGA, W. & BARAM, T. Z. (2000) Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF(1))-like immunoreactivity in the mouse brain: Light microscopy analysis using an antibody directed against the C-terminus. J. Comp Neurol. 420, 305–323.

    PubMed  Google Scholar 

  • CUMMINGS, S. & KING, J. S. (1990) Coexistence of corticotropin releasing factor and enkephalin in cerebellar afferent systems. Synapse 5, 167–174.

    PubMed  Google Scholar 

  • CUMMINGS, S., SHARP, B. & ELDE, R. (1988) Corticotropin-releasing factor in cerebellar afferent systems: A combined immunohistochemistry and retrograde transport study. J. Neurosci. 8, 543–554.

    PubMed  Google Scholar 

  • CUMMINGS, S. L., YOUNG, W. S., III, BISHOP, G. A., DESOUZA, E. B. & KING, J. S. (1989) Distribution of corticotropin releasing factor in the cerebellum and precerebellar nuclei of the opossum: A study utilizing immunohistochemistry, in situ hybridization and receptor binding. J. Comp. Neurol. 280, 501–521.

    PubMed  Google Scholar 

  • DE SOUZA, E. B. (1995) Corticotropin-releasing factor receptors: Physiology, pharmacology, biochemistry and role in central nervous system and immune disorders. Psychoneuroendocrinology 20, 789–819.

    PubMed  Google Scholar 

  • FOX, E. A. & GRUOL, D. L. (1993) Corticotropin-releasing factor suppresses the after hyperpolarization in cerebellar Purkinje neurons. Neuroscience Letters 149, 103–107.

    PubMed  Google Scholar 

  • GOTTOWIK, J., GOETSCHY, V., HENRIOT, S., KITAS, E., FLUHMAN, B., CLERC, R. G., MOREAU, J. L., MONSMA, F. J. & KILPATRICK, G. J. (1997) Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin. Neuropharmacology 36, 1439–1446.

    PubMed  Google Scholar 

  • GRIGORIADIS, D. E., HEROUX, J. A. & DE SOUZA, E. B. (1993) Characterization and regulation of corticotropinreleasing factor receptors in the central nervous system, endocrine and immunosystems. Ciba Foundation Symposium 172, 85–107.

    PubMed  Google Scholar 

  • INOUYE, M. & MURAKAMI, U. (1980) Temporal and spatial patterns of Purkinje cell formation in the mouse cerebellum. J. Comp. Neurol. 194, 499–503.

    PubMed  Google Scholar 

  • KING, J. S. & BISHOP, G. A. (2002) The distributionandcellular localiztion of CRF-R1 in the postnatal mouse cerebellum. Exp. Neurol. 178, 175–185.

    PubMed  Google Scholar 

  • KING, J. S., MADTES, JR., P. C., BISHOP, G. A. & OVERBECK, T. L. (1997) The distribution of corticotropin-releasing factor (CRF), CRF binding sites and CRF receptor mRNA in the mouse cerebellum. Progress in Brain Research 114, 55–66.

    PubMed  Google Scholar 

  • LECLERC, N., SCHWARTING, G. A., HERRUP, K., HAWKES, R. & YAMAMOTO, M. (1992) Compartmentation in mammalian cerebellum: Zebrin II and Ppath antibodies define three classes of sagittally organized bands of Purkinje cells. Proceedings of the National Acadamy of Science, USA 89, 5006–5010.

    Google Scholar 

  • LEWIS, K., LI, C., PERRIN, M. H., BLOUNT, A., KUNITAKE, K., DONALDSON, C., VAUGHAN, J., REYES, T. M., GULYAS, J., FISCHER, W., BILEZIKJIAN, L., RIVIER, J., SAWCHENKO, P. E. & VALE, W. W. (2001) Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98, 7570–7575.

    PubMed  Google Scholar 

  • LI, C., VAUGHAN, J., SAWCHENKO, P. E. & VALE, W. W. (2002) Urocortin III-immunoreactive projections in rat brain: Partial overlap with sites of type 2 corticotrophin-releasing factor receptor expression. J. Neurosci. 22, 991–1001.

    PubMed  Google Scholar 

  • LOVENBERG, T. W., LIAW, C. W., GRIGORIADIS, D. E., CLEVENGER, W., CHALMERS, D. T., DE SOUZA, E. B. & OLTERSDORF, T. (1995) Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. Proc. Natl. Acad. Sci. U.S.A. 92, 836–840.

    PubMed  Google Scholar 

  • MADTES, JR., P. C., LEE, K. H., KING, J. S. & BURRY, R. W. (2003) Corticotropin releasing factor (CRF) Protects cultured GABAergic cerebellar neurons from Ara C induced toxicity. See for Neurosci. Abst. Electronic 736.

  • MARICICH, S. M. & HERRUP, K. (1999) Pax-2 expression defines a subset of GABAergic interneurons and their precursors in the developing murine cerebellum. J. Neurobiol. 41, 281–294.

    PubMed  Google Scholar 

  • MIALE, I. L. & SIDMAN, R. L. (1961) An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp. Neurol. 4, 277–296.

    PubMed  Google Scholar 

  • MILLION, M., MAILLOT, C., SAUNDERS, P., RIVIER, J., VALE, W. & TACHE, Y. (2002) Human urocortin II, a new CRF-related peptide, displays selective CRF(2)-mediated action on gastric transit in rats. Am. J. Physiol Gastrointest. Liver Physiol 282, G34–G40.

    PubMed  Google Scholar 

  • MIYATA, M., OKADA, D., HASHIMOTO, K., KANO, M. & ITO, M. (1999) Corticotropin-releasing factor plays a permissive role in cerebellar long-term depression. Neuron 22, 763–775.

    PubMed  Google Scholar 

  • MORRIS, R. J., BEECH, J. N. & HEIZMANN, C. W. (1988) Two distinct phases and mechanisms of axonal growth shown by primary vestibular fibres in the brain, demonstrated by parvalbumin immunoshitochemistry. Neuroscience 27, 571–596.

    PubMed  Google Scholar 

  • MUGNAINI, E. & NELSON, B. J. (1989) Corticotropinreleasing factor (CRF) in the olivo-cerebellar system and the feline olivary hypertrophy. In The Olivocerebellar System in Motor Control (edited by STRATA, P.) pp. 187–197. Berlin, Heidelberg, New York: Springer-Verlag.

    Google Scholar 

  • OVERBECK, T. L. & KING, J. S. (1999) Developmental expression of corticotropin-releasing factor in the postnatal murine cerebellum. Brain Res. Dev. Brain Res. 115, 145–159.

    PubMed  Google Scholar 

  • PALKOVITS, M., LERANTH, C., GORCS, T. & YOUNG, W. S., III (1987) Corticotropin-releasing factor in the olivocerebellar tract of rats: Demonstration by light and electron microscopic immunohistochemistry and in situ hybridization histochemistry. Proceedings of the National Academy of Sciences 84, 3911–3915.

    Google Scholar 

  • PARADIES, M. A. & EISENMAN, L. E. (1993) Evidence of early topographic organization in the embryonic olivocerebellar projection: A model system for the study of pattern formation processes in the central nervous system. Developmental Dynamics 197, 125–145.

    PubMed  Google Scholar 

  • POTTER, E., BEHAN, D. P., FISCHER, W. H., LINTON, E. A., LOWRY, P. J. & VALE, W. W. (1991) Cloning and characterization of thecDNAsforhumanand rat corticotropin releasing factor-binding proteins. Nature 349, 423–426.

    PubMed  Google Scholar 

  • POWERS, R. E., DESOUZA, E. B., WALKER, L. C., PRICE, D. L., VALE, W. W. & YOUNG, W. S. I. (1987) Corticotropin-releasing factor as a transmitter in the human olivocerebellar pathway. Brain Research 415, 347–352.

    PubMed  Google Scholar 

  • SHU, S., JU, G. & FAN, L. (1988) The glucose oxidase-DABnickel method in peroxidase histochemistry of the nervous system. Neurosci. Lett. 85, 169–171.

    PubMed  Google Scholar 

  • SKELTON, K. H., OWENS, M. J. & NEMEROFF, C. B. (2000) The neurobiology of urocortin. Regulatory Peptides 93, 85–92.

    PubMed  Google Scholar 

  • VAUGHAN, J., DONALDSON, C., BITTENCOURT, J., PERRIN, M. H., LEWIS, K., SUTTON, S., CHAN, R., TURNBULL, A. V., LOVEJOY, D. & RIVIER, C. (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378, 287–292.

    PubMed  Google Scholar 

  • YAMANO, M. & TOHYAMA, M. (1994) Distribution of corticotropin releasing factor and calcitonin gene-related peptide in the developing mouse cerebellum. Neurosci. Res. 19, 387–396.

    PubMed  Google Scholar 

  • YUASA, S., KAWAMURA, K., ONO, K., YAMAKUNI, T. & TAKAHASHI, Y. (1991) Development and migration of Purkinje cells in the mouse cerebellar primordium. Anat. Embryol. (Berl) 184, 195–212.

    Google Scholar 

  • ZHANG, L. & GOLDMAN, J. E. (1996) Generation of cerebellar interneurons from dividing progenitors in white mater. Neuron 16, 47–54.

    Google Scholar 

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  1. Department of Neuroscience, The Ohio State University, 333 W. 10th Ave, Columbus, Ohio, 43210, USA

    James S. King & Georgia A. Bishop

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  1. James S. King
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  2. Georgia A. Bishop
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Correspondence to James S. King.

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King, J.S., Bishop, G.A. Localization of the type 1 corticotropin releasing factor receptor (CRF-R1) in the embryonic mouse cerebellum. J Neurocytol 32, 305–316 (2003). https://doi.org/10.1023/B:NEUR.0000010088.99394.db

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