BMP signaling mediates stem/progenitor cell-induced retina regeneration.
We identified a mechanism whereby retina regeneration in the embryonic chick can be induced by the contribution of stem/progenitor cells. We show that bone morphogenetic protein (BMP) signaling is sufficient and necessary to induce retina regeneration and that its action can be divided into two phases. By 3 days after postretinectomy (d PR), the BMP pathway directs proliferation and regeneration through the activation of Smad (canonical BMP pathway) and the up-regulation of FGF signaling by the MAPK pathway. By 7d PR, it induces apoptosis by activating p38 (a noncanonical BMP pathway) and down-regulating FGF signaling (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented, and BMP-induced regeneration can be further induced by inhibition of p38. These results unravel a mechanism for stem/progenitor cell-mediated retina regeneration, where BMP activation establishes a cross-talk with the FGF pathway and selectively activates the canonical and noncanonical BMP pathways. Retina stem/progenitor cells exist in other species, including humans. Thus, our findings provide insights on how retinal stem cells can be activated for possible regenerative therapies.
Haynes
Tracy
T
Department of Zoology, Miami University, Oxford, OH 45056, USA.
Gutierrez
Christian
C
Aycinena
Juan-Carlos
JC
Tsonis
Panagiotis A
PA
Del Rio-Tsonis
Katia
K
D000818:Animals; D017209:Apoptosis; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002642:Chick Embryo; D005123:Eye / Q000737:chemistry / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012038:Regeneration / Q000235:genetics*; D012160:Retina / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins; D005346:Fibroblast Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases