scholarly journals BMP action in skeletogenesis involves attenuation of retinoid signaling

2006 ◽  
Vol 174 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Lisa M. Hoffman ◽  
Kamal Garcha ◽  
Konstantina Karamboulas ◽  
Matthew F. Cowan ◽  
Linsay M. Drysdale ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Organ Culture ◽  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Signaling Molecules ◽  
Bmp Signaling ◽  
Retinoid Signaling ◽  
Morphogenetic Protein ◽  
Bona Fide

The bone morphogenetic protein (BMP) and growth and differentiation factor (GDF) signaling pathways have well-established and essential roles within the developing skeleton in coordinating the formation of cartilaginous anlagen. However, the identification of bona fide targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive. We have identified the gene for the retinoic acid (RA) synthesis enzyme Aldh1a2 as a principal target of BMP signaling; prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and, consequently, to reduced activation of the retinoid signaling pathway. Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits the chondrogenic stimulatory activity of BMP4. BMP4 also down-regulates Aldh1a2 expression in organ culture and, consistent with this, Aldh1a2 is actively excluded from the developing cartilage anlagens. Collectively, these findings provide novel insights into BMP action and demonstrate that BMP signaling governs the fate of prechondrogenic mesenchyme, at least in part, through regulation of retinoid signaling.

scholarly journals Inhibition of MicroRNA-302 (miR-302) by Bone Morphogenetic Protein 4 (BMP4) Facilitates the BMP Signaling Pathway

2012 ◽  
Vol 287 (46) ◽  
pp. 38656-38664 ◽  
Author(s):  
Hara Kang ◽  
Justin Louie ◽  
Alexandra Weisman ◽  
Jessica Sheu-Gruttadauria ◽  
Brandi N. Davis-Dusenbery ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein

scholarly journals Up-regulation of bone morphogenetic protein and its signaling molecules following castration of bulls and their association with intramuscular fat content in Korean cattle

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Da Jin Sol Jung ◽  
Myunggi Baik
Keyword(s):  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Glycolytic Enzyme ◽  
Bmp Signaling ◽  
Muscle Fiber Type ◽  
Mrna Levels ◽  
Korean Cattle ◽  
Morphogenetic Protein

AbstractWe evaluated whether castration affects bone morphogenetic protein 2 (BMP2) level and the expression of its signaling molecules in Korean cattle bulls. We also checked whether castration affects the expression of muscle fiber type and oxidative and glycolytic enzyme genes. Enzyme-linked immunosorbent assays revealed that steers had higher plasma BMP2 and leptin concentrations than bulls. Quantitative real-time PCR showed that steers had higher mRNA levels of the lysyl oxidase gene, a downstream target of the BMP signaling pathway, in the longissimus thoracis (LT) muscle. Steers had higher adipogenic peroxisome proliferator-activated receptor gamma and lipogenic fatty acid binding protein 4 mRNA levels in the LT than bulls. Steers had lower mRNA levels for several muscle fiber type 1 genes and fiber type 2A myosin heavy chain 2 gene than bulls. Steers had higher mRNA levels of the glycolytic enzyme phosphoglycerate kinase 1 gene than bulls. Transcript levels of oxidative enzyme genes did not differ between bulls and steers. Regression analysis revealed a positive association between plasma BMP2 levels and intramuscular fat (IMF) content in the steer group. These findings suggest that upregulation of the BMP signaling pathway in response to castration induces increased adipogenic gene expression, contributing to the increased IMF deposition observed in castrated animals.

scholarly journals The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

2013 ◽  
Vol 203 (2) ◽  
pp. 345-357 ◽  
Author(s):  
Catherine E. Winbanks ◽  
Justin L. Chen ◽  
Hongwei Qian ◽  
Yingying Liu ◽  
Bianca C. Bernardo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Muscle Mass ◽  
Muscle Wasting ◽  
Muscle Growth ◽  
Bmp Signaling ◽  
Positive Regulator ◽  
Bmp Receptors ◽  
Morphogenetic Protein

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders.

scholarly journals Synergistic interaction between the fibroblast growth factor and bone morphogenetic protein signaling pathways in lens cells

2015 ◽  
Vol 26 (13) ◽  
pp. 2561-2572 ◽  
Author(s):  
Bruce A. Boswell ◽  
Linda S. Musil
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Primary Cultures ◽  
Bmp Signaling ◽  
Fibroblast Growth ◽  
Lens Development ◽  
Morphogenetic Protein ◽  
Lens Cells ◽  
And Function

Fibroblast growth factors (FGFs) play a central role in two processes essential for lens transparency—fiber cell differentiation and gap junction–mediated intercellular communication (GJIC). Using serum-free primary cultures of chick lens epithelial cells (DCDMLs), we investigated how the FGF and bone morphogenetic protein (BMP) signaling pathways positively cooperate to regulate lens development and function. We found that culturing DCDMLs for 6 d with the BMP blocker noggin inhibits the canonical FGF-to-ERK pathway upstream of FRS2 activation and also prevents FGF from stimulating FRS2- and ERK-independent gene expression, indicating that BMP signaling is required at the level of FGF receptors. Other experiments revealed a second type of BMP/FGF interaction by which FGF promotes expression of BMP target genes as well as of BMP4. Together these studies reveal a novel mode of cooperation between the FGF and BMP pathways in which BMP keeps lens cells in an optimally FGF-responsive state and, reciprocally, FGF enhances BMP-mediated gene expression. This interaction provides a mechanistic explanation for why disruption of either FGF or BMP signaling in the lens leads to defects in lens development and function.

scholarly journals Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Stefan Washausen ◽  
Wolfgang Knabe
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Fibroblast Growth Factor ◽  
Bone Morphogenetic Protein ◽  
Bmp Signaling ◽  
Receptor Subtypes ◽  
Fibroblast Growth ◽  
Morphogenetic Protein ◽  
High Doses ◽  
Epibranchial Placodes

Placodes are ectodermal thickenings of the embryonic vertebrate head. Their descendants contribute to sensory organ development, but also give rise to sensory neurons of the cranial nerves. In mammals, the signaling pathways which regulate the morphogenesis and neurogenesis of epibranchial placodes, localized dorsocaudally to the pharyngeal clefts, are poorly understood. Therefore, we performed mouse whole embryo culture experiments to assess the impact of pan-fibroblast growth factor receptor (FGFR) inhibitors, anti-FGFR3 neutralizing antibodies or the pan-bone morphogenetic protein receptor (BMPR) inhibitor LDN193189 on epibranchial development. We demonstrate that each of the three paired epibranchial placodes is regulated by a unique combination of FGF and/or bone morphogenetic protein (BMP) signaling. Thus, neurogenesis depends on fibroblast growth factor (FGF) signals, albeit to different degrees, in all epibranchial placodes (EP), whereas only EP1 and EP3 significantly rely on neurogenic BMP signals. Furthermore, individual epibranchial placodes vary in the extent to which FGF and/or BMP signals (1) have access to certain receptor subtypes, (2) affect the production of Neurogenin (Ngn)2+ and/or Ngn1+ neuroblasts, and (3) regulate either neurogenesis alone or together with structural maintenance. In EP2 and EP3, all FGF-dependent production of Ngn2+ neuroblasts is mediated via FGFR3 whereas, in EP1, it depends on FGFR1 and FGFR3. Differently, production of FGF-dependent Ngn1+ neuroblasts almost completely depends on FGFR3 in EP1 and EP2, but not in EP3. Finally, FGF signals turned out to be responsible for the maintenance of both placodal thickening and neurogenesis in all epibranchial placodes, whereas administration of the pan-BMPR inhibitor, apart from its negative neurogenic effects in EP1 and EP3, causes only decreases in the thickness of EP3. Experimentally applied inhibitors most probably not only blocked receptors in the epibranchial placodes, but also endodermal receptors in the pharyngeal pouches, which act as epibranchial signaling centers. While high doses of pan-FGFR inhibitors impaired the development of all pharyngeal pouches, high doses of the pan-BMPR inhibitor negatively affected only the pharyngeal pouches 3 and 4. In combination with partly concordant, partly divergent findings in other vertebrate classes our observations open up new approaches for research into the complex regulation of neurogenic placode development.

scholarly journals Smad1 and Smad5 differentially regulate embryonic hematopoiesis

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3881-3890 ◽  
Author(s):  
Lisa J. McReynolds ◽  
Sunny Gupta ◽  
Maria E. Figueroa ◽  
Mary C. Mullins ◽  
Todd Evans
Keyword(s):  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Bmp Signaling ◽  
Loss Of Function ◽  
Normal Numbers ◽  
Hematopoietic Progenitors ◽  
Microarray Experiments ◽  
Morphogenetic Protein ◽  
Primitive Erythropoiesis ◽  
Related Proteins

Abstract The bone morphogenetic protein (BMP) signaling pathway regulates multiple steps of hematopoiesis, mediated through receptor-regulated Smads, including Smad1 and Smad5. Here, we use loss-of-function approaches in zebrafish to compare the roles of Smad1 and Smad5 during embryonic hematopoiesis. We show that knockdown of Smad1 or Smad5 generates distinct and even opposite hematopoietic phenotypes. Embryos depleted for Smad1 have an increased number of primitive erythrocytes, but fail to produce mature embryonic macrophages. In contrast, Smad5-depleted embryos are defective in primitive erythropoiesis, yet have normal numbers of macrophages. Loss of either Smad1 or Smad5 causes a failure in the generation of definitive hematopoietic progenitors. To investigate the mechanism behind these phenotypes, we used rescue experiments and found that Smad5 is unable to rescue the Smad1 loss-of-function phenotype, indicating that the 2 highly related proteins have inherently distinct activities. Microarray experiments revealed that the 2 proteins redundantly regulate the key initiators of the hemato-vascular program, including scl, lmo2, and gfi1. However, each also regulates a remarkably distinct genetic program, with Smad5 uniquely regulating the BMP signaling pathway itself. Our results suggest that specificity of BMP signaling output, with respect to hematopoiesis, can be explained by differential functions of Smad1 and Smad5.

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