Role for basic fibroblast growth factor (FGF-2) in tyrosine kinase (TrkB) expression in the early development and innervation of the auditory receptor: In vitro and in situ studies

A previous study showed that basic fibroblast growth factor (FGF-2) promote s the effects of brain-derived neurotrophic factor (BDNF) on migration and neurite outgrowth from the cochleovestibular ganglion (CVG:). This suggests that FGF-2 may upregulate the receptor for BDNF. Thus we have examined Trk B expression during CVG formation and otic innervation in vitro and in the chicken embryo using immunohistochemistry. Following anatomical staging acc ording to Hamburger-Hamilton, results were compared with mRNA expression in vitro using in situ hybridization. In the embryo at stage 16 (E2+) cluster s of either lightly stained or immunonegative cells occurred within the oto cyst and among those migrating to the CVG. By stage 22 (E3.5), immunostaini ng was concentrated in the CVG perikarya and invaded the processes growing into the otic epithelium but not into the rhombencephalon. Subsequently Trk B expression decreased in the perikarya and became localized in the leading processes of the fiber invading the epithelium and in the structures parti cipating in synapse formation with the hair cells. In vitro there was moder ate immunostaining and modest in situ hybridization for trkB in the neurobl asts migrating from the otocyst under control conditions. In contrast, neur oblasts previously exposed to FGF-2 exhibited accelerated migration and dif ferentiation, with increased trkB mRNA expression. Morphological differenti ation was associated with more intense immunostaining of processes than cel l bodies. Evidently TrkB shifts its expression sequentially from sites enga ged in migration, ganglion cell differentiation, axonal outgrowth, epitheli al innervation, and synapse formation. FGF-2 may promote the role of BDNF i n these developmental events by upregulating the TrkB receptor. (C) 2000 Ac ademic Press.