Regulation of avian cardiogenesis by Fgf8 signaling

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1935-1943 ◽  
Author(s):  
Burak H. Alsan ◽  
Thomas M. Schultheiss
Keyword(s):  
Ectopic Expression ◽  
Early Embryo ◽  
Bmp Signaling ◽  
Cardiac Markers ◽  
Fgf Signaling ◽  
Morphogenetic Protein ◽  
Low Concentrations ◽  
Precardiac Mesoderm ◽  
Fgf8 Signaling ◽  
Lateral Mesoderm

The avian heart develops from paired primordia located in the anterior lateral mesoderm of the early embryo. Previous studies have found that the endoderm adjacent to the cardiac primordia plays an important role in heart specification. The current study provides evidence that fibroblast growth factor (Fgf) signaling contributes to the heart-inducing properties of the endoderm. Fgf8 is expressed in the endoderm adjacent to the precardiac mesoderm. Removal of endoderm results in a rapid downregulation of a subset of cardiac markers, including Nkx2.5 and Mef2c. Expression of these markers can be rescued by supplying exogenous Fgf8. In addition, application of ectopic Fgf8 results in ectopic expression of cardiac markers. Expression of cardiac markers is expanded only in regions where bone morphogenetic protein (Bmp) signaling is also present, suggesting that cardiogenesis occurs in regions exposed to both Fgf and Bmp signaling. Finally, evidence is presented that Fgf8 expression is regulated by particular levels of Bmp signaling. Application of low concentrations of Bmp2 results in ectopic expression of Fgf8, while application of higher concentrations of Bmp2 result in repression of Fgf8 expression. Together, these data indicate that Fgf signaling cooperates with Bmp signaling to regulate early cardiogenesis.

scholarly journals BMP Signaling in Regulating Mesenchymal Stem Cells in Incisor Homeostasis

2019 ◽  
Vol 98 (8) ◽  
pp. 904-911 ◽  
Author(s):  
C. Shi ◽  
Y. Yuan ◽  
Y. Guo ◽  
J. Jing ◽  
T.V. Ho ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Cell Lineage ◽  
Craniofacial Development ◽  
Proximal Region ◽  
Bmp Signaling ◽  
Tissue Homeostasis ◽  
Fgf Signaling ◽  
Odontoblast Differentiation ◽  
Morphogenetic Protein ◽  
Mouse Incisor

Bone morphogenetic protein (BMP) signaling performs multiple essential functions during craniofacial development. In this study, we used the adult mouse incisor as a model to uncover how BMP signaling maintains tissue homeostasis and regulates mesenchymal stem cell (MSC) fate by mediating WNT and FGF signaling. We observed a severe defect in the proximal region of the adult mouse incisor after loss of BMP signaling in the Gli1+ cell lineage, indicating that BMP signaling is required for cell proliferation and odontoblast differentiation. Our study demonstrates that BMP signaling serves as a key regulator that antagonizes WNT and FGF signaling to regulate MSC lineage commitment. In addition, BMP signaling in the Gli1+ cell lineage is also required for the maintenance of quiescent MSCs, suggesting that BMP signaling not only is important for odontoblast differentiation but also plays a crucial role in providing feedback to the MSC population. This study highlights multiple important roles of BMP signaling in regulating tissue homeostasis.

scholarly journals A chordate species lacking Nodal utilizes calcium oscillation and Bmp for left–right patterning

2020 ◽  
Vol 117 (8) ◽  
pp. 4188-4198 ◽  
Author(s):  
Takeshi A. Onuma ◽  
Momoko Hayashi ◽  
Fuki Gyoja ◽  
Kanae Kishi ◽  
Kai Wang ◽  
...  
Keyword(s):  
Protein Gene ◽  
Ectopic Expression ◽  
Bmp Signaling ◽  
Calcium Oscillation ◽  
Cell Fates ◽  
Neural Genes ◽  
Morphogenetic Protein ◽  
Evolutionarily Conserved ◽  
Cell Embryo ◽  
The Right

Larvaceans are chordates with a tadpole-like morphology. In contrast to most chordates of which early embryonic morphology is bilaterally symmetric and the left–right (L–R) axis is specified by the Nodal pathway later on, invariant L–R asymmetry emerges in four-cell embryos of larvaceans. The asymmetric cell arrangements exist through development of the tailbud. The tail thus twists 90° in a counterclockwise direction relative to the trunk, and the tail nerve cord localizes on the left side. Here, we demonstrate that larvacean embryos have nonconventional L–R asymmetries: 1) L- and R-cells of the two-cell embryo had remarkably asymmetric cell fates; 2) Ca2+ oscillation occurred through embryogenesis; 3) Nodal, an evolutionarily conserved left-determining gene, was absent in the genome; and 4) bone morphogenetic protein gene (Bmp) homolog Bmp.a showed right-sided expression in the tailbud and larvae. We also showed that Ca2+ oscillation is required for Bmp.a expression, and that BMP signaling suppresses ectopic expression of neural genes. These results indicate that there is a chordate species lacking Nodal that utilizes Ca2+ oscillation and Bmp.a for embryonic L–R patterning. The right-side Bmp.a expression may have arisen via cooption of conventional BMP signaling in order to restrict neural gene expression on the left side.

Fibroblast growth factor controls the timing of Scl, Lmo2, and Runx1 expression during embryonic blood development

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1157-1166 ◽  
Author(s):  
Maggie Walmsley ◽  
David Cleaver ◽  
Roger Patient
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Bmp Signaling ◽  
Fibroblast Growth ◽  
Fgf Signaling ◽  
Pluripotent Cells ◽  
Morphogenetic Protein ◽  
Endothelial Genes ◽  
Runx1 Expression

AbstractTo program pluripotent cells into blood, a knowledge of the locations of precursors during their journey through the embryo and the signals they experience would be informative. The anterior (a) and posterior (p) ventral blood islands (VBIs) in Xenopus are derived from opposite sides of the pregastrula embryo. The aVBI goes through a “hemangioblast” state, characterized by coexpression of blood and endothelial genes at neurula stages, whereas the pVBI expresses these genes in a nonoverlapping fashion several hours later, after commitment to either a blood or an endothelial fate. We describe a novel role for fibroblast growth factor (FGF) in controlling the timing of Scl, Lmo2, and Runx1 expression in the 2 VBI compartments. Blocking FGF signaling during gastrulation expands expression at neurula stages into posterior regions. We show, by lineage labeling, explant analysis, and targeted blocking of FGF signaling, that this is due to the pVBI prematurely expressing these genes with the timing of the aVBI. In contrast, overexpression of FGF in aVBI precursors eliminates the anterior hemangioblast program. Using this information, we have recapitulated the anterior hemangioblast program in pluripotent cells in vitro by inhibiting FGF signaling in anterior mesoderm induced by activin and exposed to bone morphogenetic protein (BMP) signaling.

Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3177-3184 ◽  
Author(s):  
P.A. Wilson ◽  
G. Lagna ◽  
A. Suzuki ◽  
A. Hemmati-Brivanlou
Keyword(s):  
Cellular Response ◽  
Organizer Region ◽  
Cell Communication ◽  
Cell Types ◽  
Wing Disc ◽  
Bmp Signaling ◽  
Cell Fates ◽  
Morphogenetic Protein ◽  
Low Concentrations ◽  
Drosophila Protein

Morphogens are thought to establish pattern in early embryos by specifying several cell fates along a gradient of concentration; a well-studied example is the Drosophila protein decapentaplegic (DPP) acting in the wing disc. Recent work has established that bone morphogenetic protein 4 (BMP4), the vertebrate homologue of DPP, controls the fundamental choice between neural and epidermal fates in the vertebrate ectoderm, under the control of antagonists secreted by the organizer region of the mesoderm. We now show that BMP4 can act as a morphogen, evoking distinct responses in Xenopus ectodermal cells at high and low concentrations, in a pattern consistent with the positions of the corresponding cell types in the embryo. Moreover, this complex cellular response to extracellular BMP4 concentration does not require subsequent cell-cell communication and is thus direct, as required of a classical morphogen. We also show that the same series of cell types--epidermis, cement gland and neural tissue--can be produced by progressively inhibiting endogenous BMP signaling with specific antagonists, including the organizer factor noggin. Finally, expression of increasing doses of the signal transduction molecule Smad1 accurately reproduces the response to BMP4 protein. Since Smads have been shown to act in the nucleus, this finding implies a direct translation of extracellular morphogen concentration into transcription factor activity. We propose that a graded distribution of BMP activity controls the specification of several cell types in the gastrula ectoderm and that this extracellular gradient acts by establishing an intracellular and then nuclear gradient of Smad activity.

scholarly journals Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling

2021 ◽  
Vol 7 (7) ◽  
pp. eabf1798
Author(s):  
A. Murashima-Suginami ◽  
H. Kiso ◽  
Y. Tokita ◽  
E. Mihara ◽  
Y. Nambu ◽  
...  
Keyword(s):  
Tooth Development ◽  
Bmp Signaling ◽  
Tooth Agenesis ◽  
Tooth Regeneration ◽  
Missing Teeth ◽  
Morphogenetic Protein ◽  
Genetic Abnormalities ◽  
Direct Binding ◽  
Tooth Germs ◽  
Lipoprotein Receptor Related Protein

Uterine sensitization–associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor–related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti–USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti–USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy.

scholarly journals GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone

2020 ◽  
Vol 117 (9) ◽  
pp. 4910-4920 ◽  
Author(s):  
Joonho Suh ◽  
Na-Kyung Kim ◽  
Seung-Hoon Lee ◽  
Je-Hyun Eom ◽  
Youngkyun Lee ◽  
...  
Keyword(s):  
Bone Mass ◽  
Muscle Mass ◽  
Transforming Growth Factor ◽  
Bone Fractures ◽  
Muscle Growth ◽  
Transforming Growth Factor Β ◽  
Biochemical Properties ◽  
Bmp Signaling ◽  
Morphogenetic Protein ◽  
Perinatal Lethality

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality ofGdf11null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show thatGdf11null mice, despite significantly down-regulatingMstnexpression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed inMstnnull mice that display enhanced bone mass. Mechanistically,Mstndeletion up-regulatesGdf11expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlikeMstnnull mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.

Extracellular regulation of BMP signaling: welcome to the matrix

2017 ◽  
Vol 45 (1) ◽  
pp. 173-181 ◽  
Author(s):  
Georg Sedlmeier ◽  
Jonathan P. Sleeman
Keyword(s):  
Extracellular Matrix ◽  
Physical Properties ◽  
Bone Morphogenetic Protein ◽  
Bmp Signaling ◽  
Intracellular Level ◽  
Morphogenetic Protein ◽  
The Matrix ◽  
Mechanical Barrier

Given its importance in development and homeostasis, bone morphogenetic protein (BMP) signaling is tightly regulated at the extra- and intracellular level. The extracellular matrix (ECM) was initially thought to act as a passive mechanical barrier that sequesters BMPs. However, a new understanding about how the ECM plays an instructive role in regulating BMP signaling is emerging. In this mini-review, we discuss various ways in which the biochemical and physical properties of the ECM regulate BMP signaling.

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