Noggin-Mediated Retinal Induction Reveals a Novel Interplay Between Bone Morphogenetic Protein Inhibition, Transforming Growth Factor β, and Sonic Hedgehog Signaling.
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.
CIBIO, University of Trento, Trento, Italy.
Andrea
A
Messina
Department of Biology, University of Pisa, Pisa, Italy.
Lei
L
Lan
CIBIO, University of Trento, Trento, Italy.
Tania
T
Incitti
CIBIO, University of Trento, Trento, Italy.
Angela
A
Bozza
Department of Biology, University of Pisa, Pisa, Italy.
Massimiliano
M
Andreazzoli
Department of Biology, University of Pisa, Pisa, Italy.
Robert
R
Vignali
Scuola Normale Superiore, Pisa, Italy.
Federico
F
Cremisi
CIBIO, University of Trento, Trento, Italy.|CNR Institute of Neuroscience, Pisa, Italy.
Yuri
Y
Bozzi
CIBIO, University of Trento, Trento, Italy.|CNR Institute of Neuroscience, Pisa, Italy.
Simona
S
Casarosa
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D053823:Hedgehog Proteins; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D000099176:Noggin Protein; C558166:Shh protein, Xenopus
BMP inhibition; Forebrain patterning; Retinal induction; Sonic Hedgehog signaling; Transforming growth factor β signaling