Integration of Shh and Fgf signaling in controlling
            <i>Hox</i>
            gene expression in cultured limb cells

Rodrigues, Alan R.; Yakushiji-Kaminatsui, Nayuta; Atsuta, Yuji; Andrey, Guillaume; Schorderet, Patrick; Duboule, Denis; Tabin, Clifford J.

doi:10.1073/pnas.1620767114

Cited by 23 publications

(21 citation statements)

References 51 publications

(54 reference statements)

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“…KEGG analysis revealed four active pathways. The top pathway enriched by KEGG was Hedgehog signaling pathway, which was responsible for many aspects of vertebrate embryonic development and was disrupted in a spectrum of human tumors 14. In addition, the transport and catabolism, cell growth and death, and signal transduction cellular community might contribute significantly to the pathogenesis and progression of BLCA (Figure 4D).…”

Section: Resultsmentioning

confidence: 99%

Analysis of potential genes associated with primary cilia in bladder cancer

Du¹,

Lü²,

Sheng³

et al. 2018

CMAR

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BackgroundDysfunction of primary cilia (PC), which could influence cell cycle and modulate cilia-related signaling transduction, has been reported in several cancers. However, there is no evidence of their function in bladder cancer (BLCA). This study was performed to investigate the presence of PC in BLCA and to explore the potential molecular mechanisms underlying the PC in BLCA.Patients and methodsThe presence of PC was assessed in BLCA and adjacent non-cancerous tissues. The gene expression dataset GSE52519 was employed to obtain differentially expressed genes (DEGs) associated with PC. The mRNA expression of the DEGs were confirmed by Gene Expression Profiling Interactive Analysis. The DEGs properties and pathways were analyzed by Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Genomatix software was used to predict putative transcription factor binding sites (TFBS) in the promoter region of DEGs, and the transcription factors were achieved according to the shared TFBS, which were supported by the ChIP-Sequence data.ResultsPC were found to be reduced in BLCA tissue samples in this study. Seven DEGs were observed to be associated with PC, and gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that these DEGs exhibited the properties and functions of PC, and that the Hedgehog signaling pathway probably participated in the pathogenesis and progression of BLCA. The mRNA expression of the seven DEGs in 404 BLCA and 28 normal tissue samples were analyzed, and five DEGs including CENPF, STIL, AURKA, STK39 and OSR1 were identified. Five TFBS including CREB, E2FF, EBOX, ETSF and HOXF in the promoter region of five DEGs were calculated and the transcription factors were obtained according to the shared TFBS.ConclusionPC were found to be reduced in BLCA, and the potential molecular mechanisms of PC in BLCA helped to provide novel diagnosis and therapeutic targets for BLCA.

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Section: Resultsmentioning

confidence: 99%

Analysis of potential genes associated with primary cilia in bladder cancer

Du¹,

Lü²,

Sheng³

et al. 2018

CMAR

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“…In addition to the above experimental sets at the microscale genetic level, a different class of experiments have been performed involving the macroscale component of the BM: at the macroscopic level, morphogenetic gradients are established along the 3 axes of the embryo ( Figure 2 A) [ 20 , 21 ]. Examples of morphogenetic signals are the Sonic hedgehog (Shh) and the Fiber Growth Factors (FGF) cooperating in the limb development [ 22 ]. The signals from these gradients are transduced to the microscale level inside the cell nucleus [ 23 ].…”

Section: Morphogen Gradient Experimentsmentioning

confidence: 99%

Physical Forces May Cause the HoxD Gene Cluster Elongation

Papageorgiou

2017

Biology

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Hox gene collinearity was discovered be Edward B. Lewis in 1978. It consists of the Hox1, Hox2, Hox3 ordering of the Hox genes in the chromosome from the telomeric to the centromeric side of the chromosome. Surprisingly, the spatial activation of the Hox genes in the ontogenetic units of the embryo follows the same ordering along the anterior-posterior embryonic axis. The chromosome microscale differs from the embryo macroscale by 3 to 4 orders of magnitude. The traditional biomolecular mechanisms are not adequate to comprise phenomena at so divergent spatial domains. A Biophysical Model of physical forces was proposed which can bridge the intermediate space and explain the results of genetic engineering experiments. Recent progress in constructing instruments and achieving high resolution imaging (e.g., 3D DNA FISH, STORM etc.) enable the assessment of the geometric structure of the chromatin during the different phases of Hox gene activation. It is found that the mouse HoxD gene cluster is elongated up to 5–6 times during Hox gene transcription. These unexpected findings agree with the BM predictions. It is now possible to measure several physical quantities inside the nucleus during Hox gene activation. New experiments are proposed to test further this model.

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“…Once this cohort of limb precursors is established, continued development of the limb bud is controlled intrinsically by growth factors and patterning molecules secreted from conserved signaling centers within the limb bud itself. The apical ectodermal ridge (AER) patterns the proximal-to-distal (shoulder to digit tip) axis and secretes fibroblast growth factor signals, whilst the anterior-to-posterior axis (thumb to little finger) is patterned by the secreted morphogen, Shh, produced by cells of the ZPA [10,11]. Continued growth of the limb bud relies on establishing a positive feedback loop of FGF signaling [12].…”

Section: Limb Bud Induction Initiation and Outgrowthmentioning

confidence: 99%

The Role of Retinoic Acid in Establishing the Early Limb Bud

Feneck

Logan

2020

Biomolecules

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Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the role of RA in establishing the domain of cells that will go on to form the limb itself. Although there is some consensus on the role of RA during the earliest stages of limb formation, some controversy remains on the mechanism of RA action and the requirement for RA signaling in forming the hindlimb buds.

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Integration of Shh and Fgf signaling in controlling Hox gene expression in cultured limb cells

Cited by 23 publications

References 51 publications

Analysis of potential genes associated with primary cilia in bladder cancer

Analysis of potential genes associated with primary cilia in bladder cancer

Physical Forces May Cause the HoxD Gene Cluster Elongation

The Role of Retinoic Acid in Establishing the Early Limb Bud

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