Bone morphogenetic proteins: multifunctional regulators of vertebrate development.

Hogan, Brigid L.M.

doi:10.1101/gad.10.13.1580

Cited by 1,803 publications

(1,312 citation statements)

References 159 publications

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“…This conclusion is in agreement with a recent report (Dupé et al, 1999). The genes, bmp-2, bmp-4, and bmp-7, are all expressed in the AER at early stages of mouse limb development, and it has been proposed that they participate in controlling cell proliferation in the progress zone (Hogan, 1996). However, in the mesenchyme, these three genes have significantly different expression patterns, which suggest their involvement in different processes.…”

Section: Molecular Control Of Digit Growth and Interdigital Cell Deathsupporting

confidence: 92%

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: 92%

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

Salas‐Vidal

Valencia

Covarrubias

2001

Developmental Dynamics

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“…Many studies have shown that BMP4 is a secreted protein capable of acting over distances as a morphogen in multiple species (Harland, 1994;Re'em-Kalma et al, 1995;Dosch et al, 1997;Gerlach et al, 2000; for reviews of BMP4 activity, see Hogan, 1996;Hild et al, 2000). It is possible that DAN may act as an additional antagonist of BMP activity, complementing that of noggin, but that DAN has a specific functional role during inner ear development separate from that of its inhibition of BMPs.…”

Section: Discussionmentioning

confidence: 99%

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear

Gerlach-Bank

Cleveland

Barald

2003

Developmental Dynamics

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Bone morphogenetic proteins (BMPs) are expressed in the developing vertebrate inner ear and participate in inner ear axial patterning and the development of its sensory epithelium. BMP antagonists, such as noggin, chordin, gremlin, cerberus, and DAN (differential screening-selected gene aberrative in neuroblastoma) inhibit BMP activity and establish morphogenetic gradients during the patterning of many developing tissues and organs. In this study, the role of the BMP antagonist DAN in inner ear development was investigated. DAN-expressing cell pellets were implanted into the otocyst and the periotic mesenchyme to determine the effects of exogenous DAN on otic development. Similar to the effects on the inner ear seen after exposure of otocysts to the BMP4 antagonist noggin, semicircular canals were truncated or eliminated based upon the site of pellet implantation. Unique to the DAN implantations, however, were effects on the developing endolymphatic duct and sac. In DAN-treated inner ears, endolymphatic ducts and sacs were merged with the crus or grew into the superior semicircular canal. Both the canal and endolymphatic duct and sac effects were rescued by joint implantation of BMP4-expressing cells.

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“…The mechanism of action of extracellular regulators of embryogenesis is often portrayed to involve the direct stimulation of cell phenotypic specification. Yet it should be noted that the candidate primary regulatory events that initiate heart formation-BMP, FGF, and WNT signal transduction-seem to be overburdened in their requirements for the formation of many other tissues (Hogan, 1996;Brandon et al, 2000;Kuure et al, 2000;Huelsken and Birchmeier, 2001;Faure et al, 2002;Marie et al, 2002;Niswander, 2002). Since none of these other tissues contains cardiomyocytes, how can it be reconciled that these molecules appear to be primary signals for promoting the formation of the myocardium?…”

Section: Specification Of Precardiac Mesoderm Cellsmentioning

confidence: 99%

Stem cells and the formation of the myocardium in the vertebrate embryo

2003

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A major goal in cardiovascular biology is to repair diseased or damaged hearts with newly generated myocardial tissue. Stem cells offer a potential source of replacement myocytes for restoring cardiac function. Yet little is known about the nature of the cells that are able to generate myocardium and the conditions they require to form heart tissue. A source of information that may be pertinent to addressing these issues is the study of how the myocardium arises from progenitor cells in the early vertebrate embryo. Accordingly, this review will examine the initial events of cardiac developmental biology for insights into the identity and characteristics of the stem cells that can be used to generate myocardial tissue for therapeutic purposes. Anat Rec Part A 276A:2-12, 2004.

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Bone morphogenetic proteins: multifunctional regulators of vertebrate development.

Cited by 1,803 publications

References 159 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

DAN directs endolymphatic sac and duct outgrowth in the avian inner ear

Stem cells and the formation of the myocardium in the vertebrate embryo

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