Retinal Injury, Growth Factors, and Cytokines Converge on β-Catenin and pStat3 Signaling to Stimulate Retina Regeneration

Neuronal degeneration in the zebrafish retina stimulates Müller glia (MG) to proliferate and generate multipotent progenitors for retinal repair. Controlling this proliferation is critical to successful regeneration. Previous studies reported that retinal injury stimulates pSmad3 signaling in injury-responsive MG. Contrary to these findings, we report pSmad3 expression is restricted to quiescent MG and suppressed in injury-responsive MG. Our data indicates that Tgfb3 is the ligand responsible for regulating pSmad3 expression. Remarkably, although overexpression of either Tgfb1b or Tgfb3 can stimulate pSmad3 expression in the injured retina, only Tgfb3 inhibits injury-dependent MG proliferation; suggesting the involvement of a non-canonical Tgfb signaling pathway. Furthermore, inhibition of Alk5, PP2A or Notch signaling rescues MG proliferation in Tgfb3 overexpressing zebrafish. Finally, we report that this Tgfb3 signaling pathway is active in zebrafish MG, but not those in mice, which may contribute to the different regenerative capabilities of MG from fish and mammals.

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Growth factors and the primary cilium in BALB/c 3T3 cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128432 ◽

1987 ◽

Vol 45 ◽

pp. 830-831

Author(s):

R. W. Tucker ◽

N. S. More ◽

S. Jayaraman

Keyword(s):

Growth Factors ◽

Primary Cilium ◽

Cultured Cells ◽

Morphological Changes ◽

Calcium Ionophore ◽

Growth Stimulation ◽

Calcium Ionophore A23187 ◽

Ionophore A23187 ◽

3T3 Cells ◽

Microtubule Depolymerization

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.

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New insights into heparan sulphate biosynthesis from the study of mutant mice

Biochemical Society Symposium ◽

10.1042/bss0690047 ◽

2002 ◽

Vol 69 ◽

pp. 47-57 ◽

Cited By ~ 8

Author(s):

Catherine L. R. Merry ◽

John T. Gallagher

Keyword(s):

Growth Factors ◽

Biosynthetic Pathway ◽

Heparan Sulphate ◽

Mutant Mice ◽

Gene Products ◽

Multiple Gene ◽

Adhesion Proteins ◽

Ligand Interactions

Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS–ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st-/- mice.

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