Programmed cell death in the embryonic vertebrate limb

Zuzarte‐Luís, Vanessa; Hurlé, Juan M.

doi:10.1016/j.semcdb.2004.12.004

Cited by 129 publications

(150 citation statements)

References 91 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…11; see also diagram in Hinchliffe, 1982, Fig. 1.1 and micrographs in Zuzarte-Luis and Hurle, 2002; Fig. 1).…”

Section: Patterns Of Cell Death Differences and Similarities Betweementioning

confidence: 85%

“…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%

See 2 more Smart Citations

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

Fernandez-Teran¹,

Hinchliffe²,

Ros³

2006

Developmental Dynamics

114

104

View full text Add to dashboard Cite

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.

show abstract

“…11; see also diagram in Hinchliffe, 1982, Fig. 1.1 and micrographs in Zuzarte-Luis and Hurle, 2002; Fig. 1).…”

Section: Patterns Of Cell Death Differences and Similarities Betweementioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Fernandez-Teran¹,

Hinchliffe²,

Ros³

2006

Developmental Dynamics

114

104

View full text Add to dashboard Cite

show abstract

“…Interestingly, Msx1 and Msx2 were also expressed in the same area indicating that BMP signaling was active. Since BMP signaling is known to induce apoptosis in developing limbs (Guha et al, 2002;Zuzarte-Luis and Hurle, 2005), the ectopic BMP signaling domain provides a molecular explanation for the cell death phenotype but raises the question of how a reduced FGF signaling could result in increased Bmp expression. Remarkably, Msx2Cre;Fgf8 mutant forelimbs also show an elevation of the level of Bmp7 RNA in the anterior mesenchyme (Lewandoski et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…To investigate possible causes for the ectopic apoptosis, we analyzed the expression pattern of Bmp7, since BMP signals play an important role in inducing apoptosis in several embryonic contexts including the interdigits (Guha et al, 2002;Zuzarte-Luis and Hurle, 2005). Of note, we found that in mutant embryos Bmp7 was ectopically expressed in a domain coincident with the area of ectopic cell death (arrow in Fig.…”

Section: Abnormal Cell Death In Mutant Autopodsmentioning

confidence: 99%

The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP‐mediated cell death

Delgado

Domínguez-Frutos

Schimmang

et al. 2008

Developmental Dynamics

View full text Add to dashboard Cite

Here we analyze limb development after the conditional inactivation of Fgf8 from the epiblast, using the previously described MORE (Mox2Cre) line. This line drives variable mosaic recombination of a floxed Fgf8 allele, resulting in a small proportion of AER cells that maintain Fgf8 expression. The phenotype of Mox2Cre;Fgf8 limbs is most similar to that of Msx2Cre;Fgf8 forelimbs, indicating that a small but durable expression of FGF8 is equivalent to an early normal, but transitory, expression. This functional equivalence likely relies on the subsequent Fgf4 upregulation that buffers the differences in the pattern of Fgf8 expression between the two conditional mutants. The molecular analysis of Mox2Cre;Fgf8 limbs shows that, despite Fgf4 upregulation, they develop under reduced FGF signaling. These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod. Developmental Dynamics 237: 649 -658, 2008.

show abstract

Prenatal exposure to environmental factors and congenital limb defects

Alexander

Clark

Tuan

2016

Birth Defects Research Pt C

View full text Add to dashboard Cite

Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact. This is limited by the insufficiencies of currently available models. Specifically, in vivo approaches using guideline animal models have inherently deficient predictive power due to genomic and anatomic differences that complicate mechanistic comparisons. On the other hand, in vitro two-dimensional (2D) cell cultures, while accessible for cellular and molecular experimentation, do not reflect the three-dimensional (3D) morphogenetic events in vivo nor systemic influences. More robust and accessible models based on human cells that accurately replicate specific processes of embryonic limb development are needed to enhance limb teratogenesis prediction and to permit mechanistic analysis of the adverse outcome pathways. Recent advances in elucidating mechanisms of normal development will aid in the development of process-specific 3D cell cultures within specialized bioreactors to support multicellular microtissues or organoid constructs that will lead to increased understanding of cell functions, cell-to-cell signaling, pathway networks, and mechanisms of toxicity. The promise is prompting researchers to look to such 3D microphysiological systems to help sort out complex and often subtle interactions relevant to developmental malformations that would not be evident by standard 2D cell culture testing. Birth Defects Research (Part C) 108:243-273, 2016. © 2016 Wiley Periodicals, Inc.

show abstract

Programmed cell death in the embryonic vertebrate limb

Cited by 129 publications

References 91 publications

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

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

The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP‐mediated cell death

Prenatal exposure to environmental factors and congenital limb defects

Contact Info

Product

Resources

About