[Neuregulin/ErbB signal transduction pathway in the development of nervous system]

Neuregulins are a family of structurally-related polypeptides encoded by four distinct genes. Three isoforms of neuregulin (NRG1, 2, and 3) are highly expressed in the developing and adult brain, among which NRG1 is best characterized. NRG1 has multiple functions essential for the development of the nervous system. It promotes growth and differentiation of glial cells and regulates the migration of cerebellar granule cells along radial glial fibers. During synaptogenesis, NRG1 induces the expression of acetylcholine receptor at the neuromuscular junction and in CNS, and expression of the NMDA receptor NR2C subunit and GABAA receptors in cerebellar granule cells. Recent studies indicate that NRG receptors are densely distributed in the postsynaptic membrane, suggesting that NRGs may play an important role in synaptic plasticity. We review recent progress in studies of NRG, their functions, and signaling mechanisms.