Corticotropin releasing factor in the embryonic mouse cerebellum

Corticotropin releasing factor (CRF) is a 41 amino acid peptide that has been localized throughout the mouse cerebellum on postnatal day (P0). The wide-spread distribution of CRF within this brain region at birth suggests that it likely is present during embryonic stages of development. Thus, the intent of this study was to use immunohistochemical techniques to determine when CRF is first present in the cerebellar anlage, to analyze its distribution within the developing cerebellum, and to correlate these findings with early events in cerebellar ontogeny. CRF can first be detected in the cerebellum on embryonic day (E) 10 in scattered puncta that appear to approximate cell bodies throughout the cerebellar plate. Between E11 and E14 the number of puncta increase in the intermediate zone and more dorsal aspect of the cerebellum and decrease in the ventricular zone. At E14, in addition to the puncta, lightly immunolabeled cell bodies are observed in the ventricular zone. Just prior to birth at E17, CRF-immunoreactive varicosities distribute along the multitiered Purkinje cell layer and the intermediate zone. The CRF-positive cell bodies increase in number and intensity of staining. The majority remain within the ventricular zone, although a few also are present in the intermediate zone; it is postulated that these may be glial cells or neurons that are transiently expressing CRF. In conclusion, CRF-positive punctate elements derived from an as yet unknown source are present in the embryonic cerebellum just prior to and during the birth of Purkinje cells and nuclear neurons. The presence of this peptide at this critical stage of cerebellar development and its continued expression throughout the postnatal period of ontogeny suggests that CRF may play an important developmental role.