Noggin-Mediated Retinal Induction Reveals a Novel Interplay Between Bone Morphogenetic Protein Inhibition, Transforming Growth Factor β, and Sonic Hedgehog Signaling.

摘要: It has long been known that the depletion of bone morphogenetic protein (BMP) is one key factors necessary for development anterior neuroectodermal structures. However, precise molecular mechanisms underlie forebrain regionalization are still not completely understood. Here, we show Noggin1 involved in neural structures a dose-dependent manner. Low doses expand prosencephalic territories, while higher specify diencephalic and retinal regions at expense telencephalic areas. A similar mechanism determines ability to convert pluripotent cells or diencephalic/retinal precursors, as shown by transplant experiments analyses. At level, strong inhibition BMP signaling exerted high reinforces Nodal/transforming growth factor (TGF)β pathway, leading activation Gli1 Gli2 subsequent Sonic Hedgehog (SHH) signaling. We propose new role determining specific modulation TGFβ SHH Stem Cells 2015;33:2496–2508