Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.

During normal development oligodendrocyte precursors (OPCs) are generated in the ventral spinal cord in response to Sonic hedgehog (Shh) signalling. There is also a second, late wave of oligodendrogenesis in the dorsal spinal cord independent of Shh activity. Two signalling pathways, controlled by b...

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Autores principales:	Bilada Bilican, Christelle Fiore-Heriche, Alastair Compston, Nicholas D Allen, Siddharthan Chandran
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c7e33269d7544dfb1b7b19f36c2e793
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spelling	oai:doaj.org-article:7c7e33269d7544dfb1b7b19f36c2e7932021-11-25T06:11:16ZInduction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.1932-620310.1371/journal.pone.0002863https://doaj.org/article/7c7e33269d7544dfb1b7b19f36c2e7932008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18682850/?tool=EBIhttps://doaj.org/toc/1932-6203During normal development oligodendrocyte precursors (OPCs) are generated in the ventral spinal cord in response to Sonic hedgehog (Shh) signalling. There is also a second, late wave of oligodendrogenesis in the dorsal spinal cord independent of Shh activity. Two signalling pathways, controlled by bone morphogenetic protein and fibroblast growth factor (FGF), are active players in dorsal spinal cord specification. In particular, BMP signalling from the roof plate has a crucial role in setting up dorsal neural identity and its inhibition is sufficient to generate OPCs both in vitro and in vivo. In contrast, FGF signalling can induce OPC production from dorsal spinal cord cultures in vitro. In this study, we examined the cross-talk between mitogen-activated protein kinase (MAPK) and BMP signalling in embryonic dorsal spinal cord cultures at the SMAD1/5/8 (SMAD1) transcription factor level, the main effectors of BMP activity. We have previously shown that FGF2 treatment of neural precursor cells (NPCs) derived from rat E14 dorsal spinal cord is sufficient to generate OPCs in vitro. Utilising the same system, we now show that FGF prevents BMP-induced nuclear localisation of SMAD1-phosphorylated at the C-terminus (C-term-pSMAD1). This nuclear exclusion of C-term-pSMAD1 is dependent on MAPK activity and correlates with OLIG2 upregulation, the obligate transcription factor for oligodendrogenesis. Furthermore, inhibition of the MAPK pathway abolishes OLIG2 expression. We also show that SMAD4, which acts as a common partner for receptor-regulated Smads including SMAD1, associates with a Smad binding site in the Olig2 promoter and dissociates from it upon differentiation. Taken together, these results suggest that FGF can promote OPC generation from embryonic NPCs by counteracting BMP signalling at the Smad1 transcription factor level and that Smad-containing transcriptional complexes may be involved in direct regulation of the Olig2 promoter.Bilada BilicanChristelle Fiore-HericheAlastair CompstonNicholas D AllenSiddharthan ChandranPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e2863 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bilada Bilican Christelle Fiore-Heriche Alastair Compston Nicholas D Allen Siddharthan Chandran Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.
description	During normal development oligodendrocyte precursors (OPCs) are generated in the ventral spinal cord in response to Sonic hedgehog (Shh) signalling. There is also a second, late wave of oligodendrogenesis in the dorsal spinal cord independent of Shh activity. Two signalling pathways, controlled by bone morphogenetic protein and fibroblast growth factor (FGF), are active players in dorsal spinal cord specification. In particular, BMP signalling from the roof plate has a crucial role in setting up dorsal neural identity and its inhibition is sufficient to generate OPCs both in vitro and in vivo. In contrast, FGF signalling can induce OPC production from dorsal spinal cord cultures in vitro. In this study, we examined the cross-talk between mitogen-activated protein kinase (MAPK) and BMP signalling in embryonic dorsal spinal cord cultures at the SMAD1/5/8 (SMAD1) transcription factor level, the main effectors of BMP activity. We have previously shown that FGF2 treatment of neural precursor cells (NPCs) derived from rat E14 dorsal spinal cord is sufficient to generate OPCs in vitro. Utilising the same system, we now show that FGF prevents BMP-induced nuclear localisation of SMAD1-phosphorylated at the C-terminus (C-term-pSMAD1). This nuclear exclusion of C-term-pSMAD1 is dependent on MAPK activity and correlates with OLIG2 upregulation, the obligate transcription factor for oligodendrogenesis. Furthermore, inhibition of the MAPK pathway abolishes OLIG2 expression. We also show that SMAD4, which acts as a common partner for receptor-regulated Smads including SMAD1, associates with a Smad binding site in the Olig2 promoter and dissociates from it upon differentiation. Taken together, these results suggest that FGF can promote OPC generation from embryonic NPCs by counteracting BMP signalling at the Smad1 transcription factor level and that Smad-containing transcriptional complexes may be involved in direct regulation of the Olig2 promoter.
format	article
author	Bilada Bilican Christelle Fiore-Heriche Alastair Compston Nicholas D Allen Siddharthan Chandran
author_facet	Bilada Bilican Christelle Fiore-Heriche Alastair Compston Nicholas D Allen Siddharthan Chandran
author_sort	Bilada Bilican
title	Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.
title_short	Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.
title_full	Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.
title_fullStr	Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.
title_full_unstemmed	Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.
title_sort	induction of olig2 precursors by fgf involves bmp signalling blockade at the smad level.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/7c7e33269d7544dfb1b7b19f36c2e793
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Induction of Olig2 precursors by FGF involves BMP signalling blockade at the Smad level.

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