Disruption of G3BP1 granules promotes mammalian CNS and PNS axon regeneration.

Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in , increases the growth of spontaneously regenerating axons. Inhibition of G3BP1 by expression of its acidic or "B-domain" accelerates axon regeneration after nerve injury, bringing a potential therapeutic strategy for peripheral nerve repair. Here, we asked whether G3BP1 inhibition is a viable strategy to promote regeneration in injured mammalian central nervous system (CNS) where axons do not regenerate spontaneously.

Disruption of G3BP1 Granules Promotes Mammalian CNS and PNS Axon Regeneration.

Unlabelled: Depletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 in , increases axon regeneration in injured neurons, showing spontaneous regeneration. Inhibition of G3BP1 by expression of its acidic or 'B-domain' accelerates axon regeneration after nerve injury, bringing a potential therapeutic intervention to promote neural repair in the peripheral nervous system. Here, we asked if G3BP1 inhibition is a viable strategy to promote regeneration in injured mammalian central nervous system where axons do not regenerate spontaneously.

Retinal Ganglion Cell Axon Regeneration Requires Complement and Myeloid Cell Activity within the Optic Nerve.

Axon regenerative failure in the mature CNS contributes to functional deficits following many traumatic injuries, ischemic injuries, and neurodegenerative diseases. The complement cascade of the innate immune system responds to pathogen threat through inflammatory cell activation, pathogen opsonization, and pathogen lysis, and complement is also involved in CNS development, neuroplasticity, injury, and disease. Here, we investigated the involvement of the classical complement cascade and microglia/monocytes in CNS repair using the mouse optic nerve injury (ONI) model, in which axons arising from retinal ganglion cells (RGCs) are disrupted.

The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration.

Loss of the retinal pigment epithelium (RPE) because of dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms driving RPE regeneration.

Optic nerve regeneration: A long view.

The optic nerve conveys information about the outside world from the retina to multiple subcortical relay centers. Until recently, the optic nerve was widely believed to be incapable of re-growing if injured, with dire consequences for victims of traumatic, ischemic, or neurodegenerative diseases of this pathway. Over the past 10-20 years, research from our lab and others has made considerable progress in defining factors that normally suppress axon regeneration and the ability of retinal ganglion cells, the projection neurons of the retina, to survive after nerve injury.

Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation.

The retinal pigment epithelium (RPE) is a specialized monolayer of pigmented cells within the eye that is critical for maintaining visual system function. Diseases affecting the RPE have dire consequences for vision, and the most prevalent of these is atrophic (dry) age-related macular degeneration (AMD), which is thought to result from RPE dysfunction and degeneration. An intriguing possibility for treating RPE degenerative diseases like atrophic AMD is the stimulation of endogenous RPE regeneration; however, very little is known about the mechanisms driving successful RPE regeneration in vivo.

Using GAL4-Inducible Transgenics to Modulate Rho GTPase Activity in Zebrafish.

Rho GTPases are Ras-family G proteins that regulate many critical cellular functions. Due to their requirement during early embryonic development, investigations into the function of Rho GTPases at a tissue-specific level require inducible and spatially targeted modulation of Rho GTPase activity. Here, we describe the use of ten novel zebrafish transgenics enabling GAL4-specific expression of Rho GTPases to modulate Rho GTPase activity with spatial and temporal control.

A GAL4-inducible transgenic tool kit for the in vivo modulation of Rho GTPase activity in zebrafish.

Background: Rho GTPases are small monomeric G-proteins that play key roles in many cellular processes. Due to Rho GTPases' widespread expression and broad functions, analyses of their function during late development require tissue-specific modulation of activity. The GAL4/UAS system provides an excellent tool for investigating the function of Rho GTPases in vivo.

N-Ethylmaleimide-Sensitive Factor b (nsfb) Is Required for Normal Pigmentation of the Zebrafish Retinal Pigment Epithelium.

Purpose: Despite the number of albinism-causing mutations identified in human patients and animal models, there remain a significant number of cases for which no mutation has been identified, suggesting that our understanding of melanogenesis is incomplete. Previously, we identified two oculocutaneous albinism mutations in zebrafish, au13 and au18. Here, we sought to identify the mutated loci and determine how the affected proteins contribute to normal pigmentation of the retinal pigment epithelium (RPE).