Pax-3 is necessary for migration but not differentiation of limb muscle precursors in the mouse

Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 1017-1027 ◽  
Author(s):  
G. Daston ◽  
E. Lamar ◽  
M. Olivier ◽  
M. Goulding
Keyword(s):  
Transcription Factor ◽  
Muscle Differentiation ◽  
Precursor Cells ◽  
Limb Bud ◽  
Limb Muscle ◽  
Paired Domain ◽  
Lateral Edge ◽  
Limb Muscles ◽  
In Cells

The limb muscles of vertebrates are derived from precursor cells that migrate from the lateral edge of the dermomyotome into the limb bud. Previous studies have shown that the paired domain-containing transcription factor Pax-3 is expressed in the limb in cells that are precursors for limb muscles (Williams, B. and Ordahl, C.P. (1994) Development 120, 785–796). In splotch (Pax-3-) embryos, the limb muscles fail to develop and cells expressing Pax-3 are no longer found in the limb. In this paper we have analyzed the role of Pax-3 in the migration and subsequent differentiation of limb muscle precursors. By labeling somites adjacent to the prospective forelimb with the lipophilic dye DiI, we have shown that cells derived from these somites do not migrate into the limbs of splotch mice. The failure of limb muscle precursors to invade the limb in splotch mice is associated with the absence of c-met expression in premigratory cells, together with a change in the morphology of the ventral dermomyotome. In addition, we have shown the lateral half of somites derived from day E9.25 splotch embryos can undergo muscle differentiation when grafted into the limb bud stage 20 chick host embryos. Our results indicate that Pax-3 regulates the migration of limb muscle precursors into the limb and is not required for cells in the lateral somite to differentiate into muscle.

scholarly journals Hif-1α regulates differentiation of limb bud mesenchyme and joint development

2007 ◽  
Vol 177 (3) ◽  
pp. 451-464 ◽  
Author(s):  
Sylvain Provot ◽  
Dawn Zinyk ◽  
Yasemin Gunes ◽  
Richa Kathri ◽  
Quynh Le ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fetal Development ◽  
Adaptive Response ◽  
Conditional Knockout ◽  
Limb Bud ◽  
Low Oxygen ◽  
Joint Development ◽  
Low Oxygen Tension ◽  
Development And Differentiation

Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor Hif-1α. In this study, we provide evidence that mesenchymal condensations that give origin to endochondral bones are hypoxic during fetal development, and we demonstrate that Hif-1α is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations. To investigate the role of Hif-1α in mesenchymal condensations and in early chondrogenesis, we conditionally inactivated Hif-1α in limb bud mesenchyme using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout of Hif-1α in limb bud mesenchyme does not impair mesenchyme condensation, but alters the formation of the cartilaginous primordia. Late hypertrophic differentiation is also affected as a result of the delay in early chondrogenesis. In addition, mutant mice show a striking impairment of joint development. Our study demonstrates a crucial, and previously unrecognized, role of Hif-1α in early chondrogenesis and joint formation.

The important role of pka/creb and NF-κB/P65 signaling pathways in regulating the transcription factor AKNA in cells after the exposure of T-2 toxin

Toxicon ◽  
2019 ◽  
Vol 158 ◽  
pp. S7 ◽  
Author(s):  
Xianglian Liu ◽  
Pu Guo ◽  
Deyu Huang ◽  
Menghong Dai ◽  
Guyue Cheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Signaling Pathways ◽  
In Cells

scholarly journals Role of Mdm2 acid domain interactions in recognition and ubiquitination of the transcription factor IRF-2

2009 ◽  
Vol 418 (3) ◽  
pp. 575-585 ◽  
Author(s):  
Susanne Pettersson ◽  
Michael Kelleher ◽  
Emmanuelle Pion ◽  
Maura Wallace ◽  
Kathryn L. Ball
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
P53 Protein ◽  
E3 Ligase ◽  
Transactivation Domain ◽  
Hydrophobic Pocket ◽  
Docking Sites ◽  
Acid Domain ◽  
In Cells

Mdm2 (murine double minute 2)-mediated ubiquitination of the p53 tumour suppressor requires interaction of the ligase at two distinct binding sites that form general multiprotein-docking sites for the p53 protein. The first Mdm2-binding site resides in the transactivation domain of p53 and is an allosteric effector site for Mdm2-mediated p53 ubiquitination; the second site requires the acid domain of Mdm2 to recognize a ‘ubiquitination signal’ within p53's DNA-binding core. In order to expand on fundamental requirements for a protein to function as an Mdm2 substrate and the role of the acid domain in recognition, we have carried out a bioinformatics search for open reading frames that have homology with the Mdm2-docking sites in p53. IRF-2 [IFN (interferon) regulatory factor-2], an IFN-regulated transcription factor, has been identified as an Mdm2-binding protein and substrate requiring interactions with both the hydrophobic pocket and the acid domain of Mdm2. Mutation of either of the two Mdm2-binding sites on IRF-2 can attenuate substrate ubiquitination, confirming the requirement of a dual-site substrate interaction mechanism. Ligands that bind to the hydrophobic pocket are not sufficient to inhibit Mdm2 E3-ligase activity. Rather, acid domain-binding ligands act as E3-ligase inhibitors, lending additional support to the idea that the acid domain of Mdm2 is key to understanding its mechanism of action. The ability of Mdm2 and IRF-2 to form a complex in cells complements the biochemical assays and together establishes a novel substrate with which to develop insights into E3-ubiquitin ligase–substrate interactions in vitro and in cells.

Coordinated expression of Hoxa-11 and Hoxa-13 during limb muscle patterning

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1325-1335 ◽  
Author(s):  
M. Yamamoto ◽  
Y. Gotoh ◽  
K. Tamura ◽  
M. Tanaka ◽  
A. Kawakami ◽  
...  
Keyword(s):  
Hox Genes ◽  
Anterior Part ◽  
Posterior Part ◽  
Precursor Cells ◽  
Limb Bud ◽  
Limb Muscle ◽  
Limb Buds ◽  
Muscle Precursor ◽  
Muscle Precursor Cells ◽  
Ventral Muscle

The limb muscle precursor cells migrate from the somites and congregate into the dorsal and ventral muscle masses in the limb bud. Complex muscle patterns are formed by successive splitting of the muscle masses and subsequent growth and differentiation in a region-specific manner. Hox genes, known as key regulator genes of cartilage pattern formation in the limb bud, were found to be expressed in the limb muscle precursor cells. We found that HOXA-11 protein was expressed in the premyoblasts in the limb bud, but not in the somitic cells or migrating premyogenic cells in the trunk at stage 18. By stage 24, HOXA-11 expression began to decrease from the posterior halves of the muscle masses. HOXA-13 was expressed strongly in the myoblasts of the posterior part in the dorsal/ventral muscle masses and weakly in a few myoblasts of the anterior part of the dorsal muscle mass. Transplantation of the lateral plate of the presumptive wing bud to the flank induced migration of premyoblasts from somites to the graft. Under these conditions, HOXA-11 expression was induced in the migrating premyoblasts in the ectopic limb buds. Application of retinoic acid at the anterior margin of the limb bud causes duplication of the autopodal cartilage and transformation of the radius to the ulna, and at the same time induces duplication of the muscle pattern along the anteroposterior axis. Under these conditions, HOXA-13 was also induced in the anterior region of the ventral muscles in the zeugopod. These results suggest that Hoxa-11 and Hoxa-13 expression in the migrating premyoblasts is under the control of the limb mesenchyme and the polarizing signal(s). In addition, these results indicate that these Hox genes are involved in muscle patterning in the limb buds.

Distinct signaling molecules control Hoxa-11 and Hoxa-13 expression in the muscle precursor and mesenchyme of the chick limb bud

Development ◽  
1999 ◽  
Vol 126 (12) ◽  
pp. 2771-2783 ◽  
Author(s):  
K. Hashimoto ◽  
Y. Yokouchi ◽  
M. Yamamoto ◽  
A. Kuroiwa
Keyword(s):  
Growth Factor ◽  
Muscle Development ◽  
Hox Genes ◽  
Expression Patterns ◽  
Precursor Cells ◽  
Limb Bud ◽  
Posterior Region ◽  
Limb Muscle ◽  
Limb Mesenchyme ◽  
Myogenic Precursor

The limb muscles, originating from the ventrolateral portion of the somites, exhibit position-specific morphological development through successive splitting and growth/differentiation of the muscle masses in a region-specific manner by interacting with the limb mesenchyme and the cartilage elements. The molecular mechanisms that provide positional cues to the muscle precursors are still unknown. We have shown that the expression patterns of Hoxa-11 and Hoxa-13 are correlated with muscle patterning of the limb bud (Yamamoto et al., 1998) and demonstrated that muscular Hox genes are activated by signals from the limb mesenchyme. We dissected the regulatory mechanisms directing the unique expression patterns of Hoxa-11 and Hoxa-13 during limb muscle development. HOXA-11 protein was detected in both the myogenic cells and the zeugopodal mesenchymal cells of the limb bud. The earlier expression of HOXA-11 in both the myogenic precursor cells and the mesenchyme was dependent on the apical ectodermal ridge (AER), but later expression was independent of the AER. HOXA-11 expression in both myogenic precursor cells and mesenchyme was induced by fibroblast growth factor (FGF) signal, whereas hepatocyte growth factor/scatter factor (HGF/SF) maintained HOXA-11 expression in the myogenic precursor cells, but not in the mesenchyme. The distribution of HOXA-13 protein expression in the muscle masses was restricted to the posterior region. We found that HOXA-13 expression in the autopodal mesenchyme was dependent on the AER but not on the polarizing region, whereas expression of HOXA-13 in the posterior muscle masses was dependent on the polarizing region but not on the AER. Administration of BMP-2 at the anterior margin of the limb bud induced ectopic HOXA-13 expression in the anterior region of the muscle masses followed by ectopic muscle formation close to the source of exogenous BMP-2. In addition, NOGGIN/CHORDIN, antagonists of BMP-2 and BMP-4, downregulated the expression of HOXA-13 in the posterior region of the muscle masses and inhibited posterior muscle development. These results suggested that HOXA-13 expression in the posterior muscle masses is activated by the posteriorizing signal from the posterior mesenchyme via BMP-2. On the contrary, the expression of HOXA-13 in the autopodal mesenchyme was affected by neither BMP-2 nor NOGGIN/CHORDIN. Thus, mesenchymal HOXA-13 expression was independent of BMP-2 from polarizing region, but was under the control of as yet unidentified signals from the AER. These results showed that expression of Hox genes is regulated differently in the limb muscle precursor and mesenchymal cells.

SF/HGF is a mediator between limb patterning and muscle development

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4885-4893 ◽  
Author(s):  
M. Scaal ◽  
A. Bonafede ◽  
V. Dathe ◽  
M. Sachs ◽  
G. Cann ◽  
...  
Keyword(s):  
Muscle Development ◽  
Precursor Cells ◽  
Limb Bud ◽  
Posterior Limb ◽  
Undifferentiated State ◽  
Direction Control ◽  
Zone Of Polarizing Activity ◽  
Muscle Precursor Cells ◽  
Myogenic Precursor

Scatter factor/hepatocyte growth factor (SF/HGF) is known to be involved in the detachment of myogenic precursor cells from the lateral dermomyotomes and their subsequent migration into the newly formed limb buds. As yet, however, nothing has been known about the role of the persistent expression of SF/HGF in the limb bud mesenchyme during later stages of limb bud development. To test for a potential role of SF/HGF in early limb muscle patterning, we examined the regulation of SF/HGF expression in the limb bud as well as the influence of SF/HGF on direction control of myogenic precursor cells in limb bud mesenchyme. We demonstrate that SF/HGF expression is controlled by signals involved in limb bud patterning. In the absence of an apical ectodermal ridge (AER), no expression of SF/HGF in the limb bud is observed. However, FGF-2 application can rescue SF/HGF expression. Excision of the zone of polarizing activity (ZPA) results in ectopic and enhanced SF/HGF expression in the posterior limb bud mesenchyme. We could identify BMP-2 as a potential inhibitor of SF/HGF expression in the posterior limb bud mesenchyme. We further demonstrate that ZPA excision results in a shift of Pax-3-positive cells towards the posterior limb bud mesenchyme, indicating a role of the ZPA in positioning of the premuscle masses. Moreover, we present evidence that, in the limb bud mesenchyme, SF/HGF increases the motility of myogenic precursor cells and has a role in maintaining their undifferentiated state during migration. We present a model for a crucial role of SF/HGF during migration and early patterning of muscle precursor cells in the vertebrate limb.

The role of transcription factor Egr‐1 in IL‐1 up‐regulation of tubular CD44 expression

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.
Keyword(s):  
Transcription Factor ◽  
Cd44 Expression

Role of the transcription factor c-Jun/AP–1 in response to β-Catenin signaling in the liver

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
C Trierweiler ◽  
K Willim ◽  
HE Blum ◽  
P Hasselblatt
Keyword(s):  
Transcription Factor ◽  
Factor C

1962-P: Role of Transcription Factor TCF21 in Adipocyte Progenitor Cells of Visceral Fat

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1962-P
Author(s):  
TAKUYA MINAMIZUKA ◽  
YOSHIRO MAEZAWA ◽  
HARUHIDE UDAGAWA ◽  
YUSUKE BABA ◽  
MASAYA KOSHIZAKA ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Progenitor Cells ◽  
Visceral Fat

Inhibition of NGLY1 inactivates the transcription factor Nrf1 and potentiates proteasome inhibitor cytotoxicity

2017 ◽  
Author(s):  
Carolyn Bertozzi ◽  
Fred Tomlin ◽  
Ulla Gerling-Driessen ◽  
Yi-Chang Liu ◽  
Ryan Flynn ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Small Molecule ◽  
Proteasome Inhibitor ◽  
Activation Mechanism ◽  
Cancer Drugs ◽  
Small Molecule Library ◽  
Library Screen ◽  
In Cells

We discovered that the proteostasis modulating transcription factor Nrf1 requires cytosolic de-N-glycosylation by the N-glycanase NGly1 as part of its activation mechanism. Through a covalent small molecule library screen, we discovered an inhibitor of NGly1 that blocks Nrf1 activation in cells and potentiates the activity of proteasome inhibitor cancer drugs. The requirement of NGly1 for Nrf1 activity likely underlies several pathologies associated with a rare hereditary deficiency in NGly1.

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