Developmental Myelination

The molecular mechanisms that regulate myelination remain elusive.  The process begins with opposing ends of the Schwann cell membrane coming into contact as they wrap around the axon.  One end then slips under the other and extends forward as it encircles the axon.  The membrane continues to expand radially and also longitudinally along the axon, generating multiple concentric membrane lamellae, which later compact to form myelin.  This dynamic morphogenetic transformation is likely to reflect collaborative signaling events that are generated from multiple domains within the Schwann cell that modulate local membrane expansion and remodeling.

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One of the key molecules that regulate myelin formation in the PNS is neuregulin, an axonal protein, that binds and activates erbB2/4 receptor complex on the Schwann cells.  The receptors then activate various downstream signaling pathways that cooperate with signaling from extracellular matrix and other domains of Schwann cells to induce arrays of transcription factors that intiate the morphogenic process of myelin formation.  Our lab is currently investigating modulators of neuregulin signal and the downstream effectors in regulating myelin formation.