Reactive Oxygen Species Participate in the Control of Mouse Embryonic Cell Death

Salas‐Vidal, Enrique; Lomelı́, Hilda; Castro-Obregón, Susana; Cuervo, Rodrigo; Escalante‐Alcalde, Diana; Covarrubias, Luis

doi:10.1006/excr.1997.3828

Cited by 94 publications

(76 citation statements)

References 47 publications

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“…In mice, the interdigital tissue begins to degenerate at 13 days postcoitum (dpc) and digit individualization is completed by 14 dpc (Martin, 1990;Salas-Vidal et al, 1998;Wanek et al, 1989). Cell death in the interdigital tissue, as well as in the anterior and posterior margins of the hand plate, shows the characteristics of apoptosis such as fragmented nuclear DNA, vital dye acridine orange (AO) staining and the typical morphological features (Mori et al, 1995;Salas-Vidal et al, 1998;Zakeri et al, 1993).…”

Section: Cell Death During Interdigital Regression In Mouse Embryonicmentioning

confidence: 99%

“…Cell death in the interdigital tissue, as well as in the anterior and posterior margins of the hand plate, shows the characteristics of apoptosis such as fragmented nuclear DNA, vital dye acridine orange (AO) staining and the typical morphological features (Mori et al, 1995;Salas-Vidal et al, 1998;Zakeri et al, 1993). Since we were mainly interested in how the pattern of cell death is related to interdigital web elimination during in vivo limb development, we required minimal morphological alterations.…”

Section: Cell Death During Interdigital Regression In Mouse Embryonicmentioning

confidence: 99%

“…Since we were mainly interested in how the pattern of cell death is related to interdigital web elimination during in vivo limb development, we required minimal morphological alterations. Therefore, we took advantage of the previously reported AO staining technique as a reliable indicator of apoptosis to detect the regions of PCD in freshly dissected mouse embryonic limbs (Salas-Vidal et al, 1998). We used embryonic limbs between the S8 to S12 stage (according to Wanek et al, 1989).…”

Section: Cell Death During Interdigital Regression In Mouse Embryonicmentioning

confidence: 99%

“…We have previously used digital image superimposition to analyze embryonic limb shape changes during in vitro development (Salas-Vidal et al, 1998). In the current work, we superimposed images of the limbs shown in Fig.…”

Section: Growth Contribution To Free Digit Formationmentioning

confidence: 99%

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Differential tissue growth and patterns of cell death in mouse limb autopod morphogenesis

Salas‐Vidal

Valencia

Covarrubias

2001

Developmental Dynamics

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Programmed cell death (PCD) is considered one of the most important cellular processes in the morphogenesis of organs and tissues during animal development. Although the embryonic limb has been established as a classic model for the study of PCD, detailed studies on this process' contribution to morphogenesis are still lacking. In the present work, using modern computer-aided techniques, we estimated the contribution of PCD to mouse limb morphogenesis. For the detection of apoptotic cell death, we stained whole embryonic limbs with acridine orange or, in some instances, used the TUNEL technique, and visualized the tissues by confocal laser scanning microscopy. We found that cell death patterns are dynamic during limb development, and occur in gradients oriented with the main limb axes, anteroposterior, dorsoventral and distoproximal. Interdigital apoptosis in the autopod was initially detected at the most distal region, and then more proximally as development proceeded. Interestingly, we found that digit separation is more pronounced on the dorsal side, contrary to what is expected from the apoptotic cell distribution, which shows more abundant cell death in the ventral region. Using 2-D and 3-D models, we found that most digit individualization occurs rather by digit growth than by interdigital cell death. Therefore, digits do not mainly individualize by degeneration of preformed interdigital tissue, but probably by a dynamic balance between proliferation and cell death, reducing interdigital growth, which results in protrusion of digits. We determined the expression pattern of fgf-8 during the period of digit individualization, as the product of this gene could participate in defining the limb growth pattern. Initially, fgf-8 expression was coincident with the apical ectodermal ridge, but when cell death was first detected in the interdigits, fgf-8 expression became restricted to the tip of the growing digits. Therefore, FGF-8 could be one of the factors responsible for differential digit-interdigit growth, and might also act as a survival factor on interdigital tissue. We also found that the expression patterns of rar-␤, bmp-2, bmp-4, bmp-7, msx-1, and msx-2 genes, proposed to be involved in the activation of interdigital cell death, did not overlap with, or were not highly expressed in the major zones of cell death in the developing limb.

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Section: Cell Death During Interdigital Regression In Mouse Embryonicmentioning

confidence: 99%

Section: Cell Death During Interdigital Regression In Mouse Embryonicmentioning

confidence: 99%

Section: Cell Death During Interdigital Regression In Mouse Embryonicmentioning

confidence: 99%

Section: Growth Contribution To Free Digit Formationmentioning

confidence: 99%

See 2 more Smart Citations

Differential tissue growth and patterns of cell death in mouse limb autopod morphogenesis

Salas‐Vidal

Valencia

Covarrubias

2001

Developmental Dynamics

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“…In terms of exploring the mechanisms whereby sildenafil might protect only cardiomyocytes while allowing adriamycin to target the breast tumor cell, it is important to recognize that the foundation for the differential effects is likely to be doxorubicin acting as a topoisomerase II poison in tumor cells (5) while its toxicity to the heart is through the generation of free radicals (9,10). However, our studies raise some questions relating to this paradigm.…”

Section: Studies In Cardiomyocytesmentioning

confidence: 99%

Sildenafil and Phosphofiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumors to Doxrubicin

Gewirtz¹

2008

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTIn our studies of the interaction between sildenafil and adriamycin in breast tumor cells and cardiomyocytes, we have made the following observations. In breast tumor cells: 1. Sildenafil fails to protect various breast tumor cell lines against the toxicity of adriamycin. 2. Sildenafil moderately enhances the response to adriamycin in breast tumor cells .3. Sildenafil does not alter the extent of DNA damage induced by adriamycin in breast tumor cells. 4. Adriamycin promotes autophagy in breast tumor cells. 5. Sildenafil appears to increase sensitivity to irradiation in breast tumor cells. In cardiomyocytes: 1. Questions are raised relating to the role of reactive oxygen in the cardiotoxicity of adriamycin. 2. The combination of Herceptin with taxol or adriamycin is relatively toxic in cardiomyocytes. Based on these observations, we propose to further explore the basis for adriamycin cardiotoxicity as well as examining the capacity of sildenafil to protect the heart cells from the combination of Herceptin with Adriamycin and with taxol. We will evaluate the influence of sildenafil on autophagy and senescence in both breast tumor cells and cardiomyocytes. We will pursue the unexpected finding that sildenafil appears to increase sensitivity to radiation in the breast tumor cells by attempting to understand the mechanistic basis for this observation. We will also assess the impact of sildenafil on radiation sensitivity in the cardiomyocyte. These proposed studies are of significance because the heart is known to incur damage during irradiation of the breast during therapy for breast cancer.

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Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene

Theis

Wit

Schlaeger

et al. 2000

genesis

162

187

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The murine gap junction protein connexin43 (Cx43) is expressed in blood vessels, with vastly different contribution by endothelial and smooth muscle cells. We have used the Cre recombinase under control of TIE2 transcriptional elements to inactivate a floxed Cx43 gene specifically in endothelial cells. Cre-mediated deletion led to replacement of the Cx43 coding region by a lacZ reporter gene. This allowed us to monitor the extent of deletion and to visualize the endothelial expression pattern of Cx43. We found widespread endothelial expression of the Cx43 gene during embryonic development, which became restricted largely to capillaries and small vessels in all adult organs examined. Mice lacking Cx43 in endothelium did not exhibit altered blood pressure, in contrast to mice deficient in Cx40. Our results show that lacZ activation after deletion of the target gene allows us to determine the extent of cell type-specific deletion after phenotypical investigation of the same animal.

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Reactive Oxygen Species Participate in the Control of Mouse Embryonic Cell Death

Cited by 94 publications

References 47 publications

Differential tissue growth and patterns of cell death in mouse limb autopod morphogenesis

Differential tissue growth and patterns of cell death in mouse limb autopod morphogenesis

Sildenafil and Phosphofiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumors to Doxrubicin

Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene

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