Morphological Diversity of the Avian Foot Is Related with the Pattern ofmsxGene Expression in the Developing Autopod

Gañán, Yolanda; Macias, D.; Basco, Ricardo D.; Merino, Ramón; Hurlé, Juan M.

doi:10.1006/dbio.1997.8843

Cited by 90 publications

(103 citation statements)

References 31 publications

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“…We show that fgf-8 expression became restricted to the tip of digits at the onset of interdigital apoptosis. The same fgf-8 expression pattern has been shown in developing chick limbs (Gañ an et al, 1998). Therefore, an AER-like function remains in the digits and disappears from the interdigits, and is potentially responsible for maintaining digit growth.…”

Section: Molecular Control Of Digit Growth and Interdigital Cell Deathsupporting

confidence: 59%

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: Molecular Control Of Digit Growth and Interdigital Cell Deathsupporting

confidence: 59%

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

Salas‐Vidal

Valencia

Covarrubias

2001

Developmental Dynamics

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“…MSX1 is known to be involved in cell proliferation and apoptotic signal pathways downstream of NF-B, and induction of NF-B represses MSX1 (55). Furthermore, MSX-1 gene expression correlates with the degree of apoptosis in models for apoptosis, and reduced levels of MSX-1 gene expression are correlated with an induction in apoptosis (56). MAD2 is a mitotic checkpoint protein up-regulated between non-recurrent primary prostate cancers and highly proliferative metastatic prostate cancers (57), and embryonic cells of MAD2 knockout mice lack accurate chromosome assembly, undergo apoptosis, and are non-viable (58).…”

Section: Discussionmentioning

confidence: 99%

Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells

Bottone

Martinez

Collins

et al. 2003

Journal of Biological Chemistry

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The mechanisms underlying the anti-tumorigenic properties of cyclooxygenase inhibitors are not well understood. One novel hypothesis is alterations in gene expression. To test this hypothesis sulindac sulfide, which is used to treat familial adenomatous polyposis, was selected to detect gene modulation in human colorectal cells at physiological concentrations with microarray analysis. At micromolar concentrations, sulindac sulfide stimulated apoptosis and inhibited the growth of colorectal cancer cells on soft agar. Sulindac sulfide (10 M) altered the expression of 65 genes in SW-480 colorectal cancer cells, which express cyclooxygenase-1 but little cyclooxygenase-2. A more detailed study of 11 genes revealed that their expression was altered in a time-and dose-dependent manner as measured by real-time RT-PCR. Northern analysis confirmed the expression of 9 of these genes, and Western analysis supported the conclusion that sulindac sulfide altered the expression of these proteins. Cyclooxygenase-deficient HCT-116 cells were more responsive to sulindac sulfide-induced gene expression than SW-480 cells. However, this response was diminished in HCT-116 cells overexpressing cyclooxygenase-1 compared with normal HCT-116 cells suggesting the presence of cyclooxygenase attenuates this response. However, prostaglandin E 2 , the main product of cyclooxygenase, only suppressed the sulindac sulfide-induced expression of two genes, with little known biological function while it modulated the expression of two more. The most likely explanation for this finding is the metabolism of sulindac sulfide to inactive metabolites by the peroxidase activity of cyclooxygenase. In conclusion, this is the first report showing sulindac sulfide, independent of cyclooxygenase, altered the expression of several genes possibly linked to its anti-tumorigenic and pro-apoptotic activity.

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“…To provide a good visualization of the shape of the limb, for each stage we present a picture of the limb hybridized for Msx2. Although the correlation between Msx2 and cell death has been extensively suggested (Krabbenhoft and Fallon, 1992;Graham et al, 1994;Gañ an et al, 1998), the choice of Msx2 was arbitrary, based solely on its peripheral pattern of expression that permits an excellent visualization of the shape of the limb.…”

Section: Cell Death and Proliferation In The Chick Wing Budmentioning

confidence: 99%

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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Morphological Diversity of the Avian Foot Is Related with the Pattern ofmsxGene Expression in the Developing Autopod

Cited by 90 publications

References 31 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

Gene Modulation by the Cyclooxygenase Inhibitor, Sulindac Sulfide, in Human Colorectal Carcinoma Cells

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

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