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 sta ges of neuronal development. Shortly after differentiating from progen itor cells, sensory neurons undergo a distinct morphological change; i nitially they have small, spindle-shaped, phase-dark cell bodies that become large, spherical, and phase-bright. Early sensory neurons cultu red from the trigeminal ganglia of bcl-2(-/-) embryos at embryonic day 11 (E11) and E12 underwent this change more slowly than trigeminal ne urons of wild-type embryos of the same ages. The delay was not attribu table to the well documented role of Bcl-2 in preventing apoptosis, be cause Bcl-2-deficient early sensory neurons survived as well as wild-t ype 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 di d not cause a uniform delay in the developmental program of sensory ne urons, because the time course of nerve growth factor receptor express ion (both trkA and p75) was unaffected in the trigeminal neurons of bc l-2(-/-) embryos. These findings indicate that Bcl-2 expression is req uired for the normal progression of a particular early maturational ch ange in embryonic sensory neurons.