AXONAL INTERACTIONS REGULATE SCHWANN-CELL APOPTOSIS IN DEVELOPING PERIPHERAL-NERVE - NEUREGULIN RECEPTORS AND THE ROLE OF NEUREGULINS

Programmed cell death during development resulting from the lack of ap propriate survival factors has been demonstrated in both neurons and o ligodendrocytes and occurs mostly in the form of apoptosis. We now dem onstrate that Schwann cells in the rat sciatic nerve undergo apoptosis during early postnatal development and that the amount of apoptosis i s markedly increased by axotomy. The apoptotic Schwann cells express t he low-affinity nerve growth factor receptor but not myelin-related pr oteins, indicating that they are in the premyelinating state. Apoptosi s resulting from normal development or from axotomy can be inhibited m arkedly by exogenous neuregulin. Consistent with this, the neuregulin receptor components erbB2 and erbB3 are expressed and phosphorylated i n developing sciatic nerve. These data suggest that Schwann cell numbe r in developing peripheral nerve is regulated by apoptosis through com petition for axonally derived neuregulin.