The transcription factor Egr3 modulates sensory axon-myotube interactions during muscle spindle morphogenesis

The Egr family of zinc-finger transcription factors, consisting of Egr1, Eg r2, Egr3, and Egr4 are involved in cellular growth and differentiation. Adu lt Egr3-deficient mice are ataxic and lack muscle spindle proprioceptors th at normally develop at the sites of Ia afferent-myotube contacts during emb ryogenesis. To resolve whether spindles form and then degenerate, or whethe r they never form in the absence of Egr3, we examined the spatiotemporal ex pression of Egr3 relative to spindle development. In wild type mice, Egr3 w as expressed in developing myotubes shortly after they were innervated by I a afferents and its expression was controlled by innervation because it dis sipated following nerve transection. In Egr3-deficient mice, myotubes recei ved Ia afferent innervation and assembled normally into spindles during emb ryogenesis. However, newborn Egr3-deficient spindles had few internal myonu clei in intrafusal fibers and thin capsules. Moreover, slow-developmental m yosin heavy chain was not induced in embryonic Egr3-deficient spindles sugg esting that impairments in differentiation were present before they could b e detected morphologically. After birth, sensory and motor innervation with drew from the Egr3-deficient spindles, and the spindles disassembled. In sp ite of the spindle disassembly and retraction of afferents from muscles, th e cell bodies of proprioceptive neurons within dorsal root ganglia were ret ained. We conclude that Egr3 has an essential role in regulating genes requ ired for the transformation of undifferentiated myotubes into intrafusal fi bers, and hence for the phenotypic differentiation of spindles. (C) 2001 Ac ademic Press.