A
growth factor may have different actions depending on developmental stage. We investigated this phenomenon in the interactions of
fibroblast growth factor 2 (
FGF2) and
neurotrophins on cochlear
ganglion (CG) development. The portions of the otocyst fated to form the CG and cochlear epithelium were cocultured at embryonic day 11 (E11). Cultures were divided into groups fed with defined medium, with or without
FGF2 and
neurotrophin supplements, alone or in combination, for 7 days. We measured the number of migrating neuroblasts and distances migrated, neurite outgrowth, and axonlike processes. We used immunohistochemistry to locate
neurotrophin 3 (NT3) and its high-affinity
receptor (TrkC) in the auditory system, along with
FGF2 and its R1 receptor, at comparable developmental stages in vitro and in situ from E11 until birth (P1) in the precursors of hair cells, support cells, and CG cells. Potential sites for interaction were localized to the nucleus, perikaryal cytoplasm, and cell surfaces, including processes and growth cones. Time-lapse imaging and quantitative measures support the hypothesis that
FGF2 alone or combined with
neurotrophins promotes migration and neurite outgrowth. Synergism or antagonism between NT3 and other factors suggest interactions at the receptor level. Formation of axons, endings, and synaptic vesicle
protein 2 were increased by interactions of NT3 and
FGF2. Similar experiments with a mutant overexpressor for
FGF2 suggest that endogenous
FGF2 supports migration and neurite outgrowth of CG neuroblasts as well as proliferation, leading to accelerated development. The findings suggest interactive and sequential roles for
FGF2 and NT3.