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

Andrea Messina, Lei Lan, Tania Incitti, Angela Bozza, Massimiliano Andreazzoli, Robert Vignali, Federico Cremisi, Yuri Bozzi, Simona Casarosa

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)2496-2508
Number of pages13
JournalSTEM CELLS
Volume33
Issue number8
DOIs
StatePublished - Aug 1 2015

Keywords

  • BMP inhibition
  • Forebrain patterning
  • Retinal induction
  • Sonic Hedgehog signaling
  • Transforming growth factor β signaling

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