Levels of Gli3 repressor correlate with<i>Bmp4</i>expression and apoptosis during limb development

Bastida, Maria Félix; Delgado, M. Dolores; Wang, Baolin; Fallon, John F.; Fernandez-Teran, Marian; Ros, María A.

doi:10.1002/dvdy.20121

Cited by 58 publications

(28 citation statements)

References 72 publications

(107 reference statements)

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“…This finding calls for a role for Shh to ensure survival and growth of the posterior mesenchyme. Indeed, inactivation of Shh results in a significant increase in apoptosis, concentrated paradoxically in the anterior mesenchyme, similarly to ZPA excision in the chick (Todt andFallon, 1987: Chiang et al, 2001;Bastida et al, 2004). Interestingly, while the chick has a posterior necrotic zone overlapping the posterior of the ZPA, mouse limb buds have no comparable zone of cell death (Saunders and Fallon, 1967;Harfe et al, 2004).…”

Section: Downstream Shh: Life and Death In The Limb Fieldmentioning

confidence: 99%

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Robert

Lallemand

2006

Developmental Dynamics

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The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results. Developmental Dynamics 235:2337-2352, 2006.

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Section: Downstream Shh: Life and Death In The Limb Fieldmentioning

confidence: 99%

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Robert

Lallemand

2006

Developmental Dynamics

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“…It has been suggested that the ANZ could expand after a drop in the level of the morphogen diffusing from the zone of polarizing activity (Hinchliffe, 1981). Indeed the anterior mesoderm in chick requires the posterior mesoderm to survive and dies when it is deprived of Shh signaling (Bastida et al, 2004).…”

Section: Morphogenetic Significance Of Areas Of Cell Deathmentioning

confidence: 99%

“…It is probably controlled by many signals (e.g., Bmp, Shh, Fgf, Dkk; Zuzarte-Luis and Hurle, 2002Hurle, , 2005Bastida et al, 2004;Grotewold and Ruther, 2002) that result in distinct temporal and spatial areas in which cells die. The regions of cell death in the avian developing limb were extensively studied and mapped in classic studies, mostly in the chick wing (Saunders et al, 1962;Hinchliffe and Ede, 1973).…”

Section: Introductionmentioning

confidence: 99%

“…Lately, much attention has been paid to the study of the molecular mechanisms that trigger and control the process of programmed cell death during limb development (ZuzarteLuis and Hurle, 2002Hurle, , 2005Bastida et al, 2004;Grotewold and Ruther, 2002), however, accounts of the spatiotemporal distribution of the areas of cell death during limb development often appear confused between birds and mammals, and between fore-and hindlimbs. Equally, although much effort has been made to unravel the molecular basis of cell proliferation, few studies have been devoted to the analysis of the spatiotemporal patterns of proliferation during limb bud development.…”

Section: Introductionmentioning

confidence: 99%

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Birth and death of cells in limb development: A mapping study

Fernandez-Teran¹,

Hinchliffe²,

Ros³

2006

Developmental Dynamics

114

104

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Cell death and cell proliferation are basic cellular processes that need to be precisely controlled during embryonic development. The developing vertebrate limb illustrates particularly well how correct morphogenesis depends on the appropriate spatial and temporal balance between cell death and cell proliferation. Precise knowledge of the patterns of cell proliferation and cell death during limb development is required to understand how their modifications may contribute to the generation of the great diversity of limb phenotypes that result from spontaneous mutations or induced genetic manipulations. We have performed a comprehensive analysis of the patterns of cell death, assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL), and cell proliferation, assayed by anti-phosphorylated histone H3 immunohistochemistry, in consecutive sections of forelimbs and hindlimbs covering an extensive period of chick and mouse limb development. Our results confirm and expand previous reports and show common and specific areas of cell death for each species. Mitotic cells were found scattered in a uniform distribution across the early limb bud, with the exception of the areas of cell death in which mitotic cells were scarce. At later stages, mitotic cells were seen more abundantly in the digital tips. The aim of the present study was to satisfy the need for organized data sets describing these processes, which will allow the side-by-side comparison between the two major model organisms of limb development, i.e., the mouse and the chick.

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“…In accordance with this, Shh overexpression in the human gastric adenocarcinoma cell line, AGS, promoted growth significantly compared with vector control-transfected cells in serum free medium ( Figure 4C, Po0.0001). Apoptotic potential was determined by examining bcl-2 expression, a known down-stream, antiapoptotic factor associated with hedgehog signalling (Bastida et al, 2004) and expression was confirmed in the stroma associated with metaplastic lesions in infected but not non-infected mice ( Figure 4B). The stroma was subjected to LCM and it was shown that whereas Shh was not expressed, Shh target genes, Ptch-1 and Gli-1, were co-expressed in the stroma surrounding Shh-expressing lesions in H. felis-infected InsGas mice ( Figure 4D).…”

Section: Enhanced Cell Growth and Antiapoptotic Activity In Advanced mentioning

confidence: 99%

De-regulation of the sonic hedgehog pathway in the InsGas mouse model of gastric carcinogenesis

et al. 2007

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This study investigated sonic hedgehog (Shh) signalling in gastric metaplasia in the insulin-gastrin (InsGas) hypergastrinaemic mouse þ /À Helicobacter felis (H. felis) infection. Sonic hedgehog gene and protein expression was reduced in pre-metaplastic lesions from non-infected mice (90% gene reduction, Po0.01) compared to normal mucosa. Sonic hedgehog was reactivated in gastric metaplasia of H. felis-infected mice (3.5-fold increase, Po0.01) compared to pre-metaplastic lesions. Additionally, the Shh target gene, gliomaassociated oncogene (Gli)-1, was significantly reduced in the gastric glands of InsGas mice (75% reduction, Po0.05) and reactivated with H. felis infection (Po0.05, base of glands, Po0.01 stroma of metaplastic glands). The ability of H. felis to activate the Shh pathway was investigated by measuring the effect of target cytokine, interleukin-8 (IL-8), on Shh expression in AGS and MGLVA1 cells, which was shown to induce Shh expression at physiological concentrations. H. felis induced the expression of NF-kB in inflammatory infiltrates in vivo, and the expression of the IL-8 mouse homologue, protein KC, in inflammatory infiltrates and metaplastic lesions. Sonic hedgehog pathway reactivation was paralleled with an increase in proliferation of metaplastic lesions (15.75 vs 4.39% in infected vs non-infected mice, respectively, Po0.001). Furthermore, Shh overexpression increased the growth rate of the gastric cancer cell line, AGS. The antiapoptotic protein, bcl-2, was expressed in the stroma of infected mice, along with a second Shh target gene, patched-1 (P ¼ 0.0001, stroma of metaplastic gland). This study provides evidence suggesting reactivation of Shh signalling from pre-metaplastic to advanced metaplastic lesions of the stomach and outlines the importance of the Shh pathway as a potential chemoprophylactic target for gastric carcinogenesis.

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Levels of Gli3 repressor correlate withBmp4expression and apoptosis during limb development

Cited by 58 publications

References 72 publications

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Anteroposterior patterning in the limb and digit specification: Contribution of mouse genetics

Birth and death of cells in limb development: A mapping study

De-regulation of the sonic hedgehog pathway in the InsGas mouse model of gastric carcinogenesis

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