Localization of the type 1 corticotropin releasing factor receptor (CRF-R1) in the embryonic mouse cerebellum.
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.
King
James S
JS
Department of Neuroscience, The Ohio State University, 333 W. 10th Ave. Columbus, Ohio 43210, USA. king.11@osu.edu
Bishop
Georgia A
GA
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus; D005865:Gestational Age; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D051379:Mice; D051762:PAX2 Transcription Factor; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000099052:CRF Receptor, Type 1
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D018019:Receptors, Corticotropin-Releasing Hormone; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone