Bcl-2 accelerates the maturation of early sensory neurons.

Bcl-2 is a cytoplasmic protein that blocks apoptosis in a wide variety of cell types. Here we report a novel role for Bcl-2 in the early stages of neuronal development. Shortly after differentiating from progenitor cells, sensory neurons undergo a distinct morphological change; initially they have small, spindle-shaped, phase-dark cell bodies that become large, spherical, and phase-bright. Early sensory neurons cultured from the trigeminal ganglia of bcl-2-/- embryos at embryonic day 11 (E11) and E12 underwent this change more slowly than trigeminal neurons of wild-type embryos of the same ages. The delay was not attributable to the well documented role of Bcl-2 in preventing apoptosis, because Bcl-2-deficient early sensory neurons survived as well as wild-type neurons. Accordingly, there was a significantly smaller number of the more mature type of neuron in the early trigeminal ganglia of bcl-2-/- embryos, yet the number of neurons in the trigeminal ganglia of bcl-2-/- and wild-type embryos was similar. The absence of Bcl-2 did not cause a uniform delay in the developmental program of sensory neurons, because the time course of nerve growth factor receptor expression (both trkA and p75) was unaffected in the trigeminal neurons of bcl-2-/- embryos. These findings indicate that Bcl-2 expression is required for the normal progression of a particular early maturational change in embryonic sensory neurons.