Corticotropin releasing factor (CRF) is a 41 amino acid peptide that has be
en localized throughout the mouse cerebellum on postnatal day (PO). The wid
espread distribution of CRF within this brain region at birth suggests that
it likely is present during embryonic stages of development. Thus, the int
ent of this study was to use immunohistochemical techniques to determine wh
en CRF is first present in the cerebellar anlage, to analyze its distributi
on within the developing cerebellum, and to correlate these findings with e
arly events in cerebellar ontogeny. CRF can first be detected in the cerebe
llum on embryonic day (E) 10 in scattered puncta that appear to approximate
cell bodies throughout the cerebellar plate. Between Ell and E14 the numbe
r 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 th
e puncta, lightly immunolabeled cell bodies are observed in the ventricular
zone. Just prior to birth at E17, CRF-immunoreactive varicosities distribu
te 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 prese
nt in the intermediate zone; it is postulated that these may be glial cells
or neurons that are transiently expressing CRF. In conclusion, CRF-positiv
e punctate elements derived from an as yet unknown source are present in th
e embryonic cerebellum just prior to and during the birth of Purkinje cells
and nuclear neurons. The presence of this peptide at this critical stage o
f cerebellar development and its continued expression throughout the postna
tal period of ontogeny suggests that CRF may play an important developmenta
l role. (C) 1999 Academic Press.