Inhibition of FGF signaling converts dorsal mesoderm to ventral mesoderm in early Xenopus embryos

Lee, Sung‐Young; Lim, Soo-Kyung; Cha, Sang‐Wook; Yoon, Jaeho; Lee, Seung Hwan; Lee, Hyun‐Shik; Park, Jae-Bong; Lee, Jae Yong; Kim, Sung Chan; Kim, Jaebong

doi:10.1016/j.diff.2011.05.009

Cited by 11 publications

(21 citation statements)

References 39 publications

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“…The induction of paraxial mesoderm fate from NMPs in vitro by FGF signaling alone suggested that this factor may be important for paraxial mesoderm patterning. Indeed, during gastrulation, FGF signaling promotes paraxial mesoderm fates ( Fürthauer et al, 1997 ; 2004 ; Lee et al, 2011 ), and is active in the post-gastrulation paraxial presomitic mesoderm ( Dubrulle et al, 2001 ; Sawada et al, 2001 ). Interestingly, during posterior axial extension, BMP ligands are expressed in ventral posterior tissues juxtaposed to the presomitic mesoderm ( Martínez-Barberá et al, 1997 ).…”

Section: Resultsmentioning

confidence: 99%

BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity

Row

Pegg

Kinney

et al. 2018

eLife

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The mesodermal germ layer is patterned into mediolateral subtypes by signaling factors including BMP and FGF. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF-mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer.

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Section: Resultsmentioning

confidence: 99%

BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity

Row

Pegg

Kinney

et al. 2018

eLife

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“…In zebrafish, FGFs were found to regulate DV patterning of the mesoderm rather than its induction, i.e., the third signal of the 3SM rather than the second [ 30 , 31 ]. A role for FGFs in DV patterning has recently also been suggested in Xenopus [ 32 ].…”

Section: Secreted Factors As Candidate Mesendoderm Inducersmentioning

confidence: 99%

“…The homeobox genes vent1 / 2, PV.1 and vox are all expressed in the ventrolateral mesoderm; they are induced by ventralising BMP signalling; and they induce BMPs, antagonise organiser genes and ventralise embryos upon overexpression [ 32 , 205 – 208 ]. Injections of dominant-negative forms of these factors into ventral blastomeres of Xenopus embryos frequently result in the induction of a secondary organiser and, subsequently, body axis duplication [ 226 , 227 ].…”

Section: Transcription Factors In Germ Layer Specificationmentioning

confidence: 99%

Molecular specification of germ layers in vertebrate embryos

Kiecker

Bates

Bell

2015

Cell. Mol. Life Sci.

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In order to generate the tissues and organs of a multicellular organism, different cell types have to be generated during embryonic development. The first step in this process of cellular diversification is the formation of the three germ layers: ectoderm, endoderm and mesoderm. The ectoderm gives rise to the nervous system, epidermis and various neural crest-derived tissues, the endoderm goes on to form the gastrointestinal, respiratory and urinary systems as well as many endocrine glands, and the mesoderm will form the notochord, axial skeleton, cartilage, connective tissue, trunk muscles, kidneys and blood. Classic experiments in amphibian embryos revealed the tissue interactions involved in germ layer formation and provided the groundwork for the identification of secreted and intracellular factors involved in this process. We will begin this review by summarising the key findings of those studies. We will then evaluate them in the light of more recent genetic studies that helped clarify which of the previously identified factors are required for germ layer formation in vivo, and to what extent the mechanisms identified in amphibians are conserved across other vertebrate species. Collectively, these studies have started to reveal the gene regulatory network (GRN) underlying vertebrate germ layer specification and we will conclude our review by providing examples how our understanding of this GRN can be employed to differentiate stem cells in a targeted fashion for therapeutic purposes.

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“…We hypothesised that proNodal might exert its non-canonical effect via an interaction(s) with a second signalling pathway. Previous studies in other tissues have suggested co-operative actions between Nodal and FGF ( Beck et al, 2002 ; Guzman-Ayala et al, 2004 ; Lee et al, 2011 ; Mathieu et al, 2004 ; Vallier et al, 2005 ; Yokota et al, 2003 ), and FGF receptors and signal pathway components are expressed in and around prechordal mesoderm over HH st4-st13 ( Karabagli et al, 2002 ; Lunn et al, 2007 ; Nishita et al, 2011 ; Walshe and Mason, 2000 ). This led us to test the hypothesis that proNodal exerts its actions via an FGF signal pathway component.…”

Section: Resultsmentioning

confidence: 99%

“…Our studies do not distinguish whether proNodal-FGFR3 directly maintains Shh expression, or whether proNodal-FGFR3 operates indirectly, for instance, antagonising a pathway that represses Shh. Previous studies have revealed antagonistic interactions between Nodal and BMP signalling pathways ( Lee et al, 2011 ; Lenhart et al, 2013 ; Yang et al, 2010 ; Yeo and Whitman, 2001 ) and BMP ligands are expressed in the prechordal mesoderm ( Vesque et al, 2000 ). Bmp7 is expressed particularly strongly from HH st6/7 and maintained through st8-st13 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

et al. 2015

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The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we show that in the embryonic chick, Shh is expressed transiently in prechordal mesoderm, and is governed by unprocessed Nodal. Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained through canonical signalling, Nodal signals through a non-canonical route to maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co-immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression. Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3 siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA to prechordal mesoderm in vivo results in premature Shh downregulation without affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3 signalling is downregulated.

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Inhibition of FGF signaling converts dorsal mesoderm to ventral mesoderm in early Xenopus embryos

Cited by 11 publications

References 39 publications

BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity

BMP and FGF signaling interact to pattern mesoderm by controlling basic helix-loop-helix transcription factor activity

Molecular specification of germ layers in vertebrate embryos

ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

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