Evidence for regulation of growth, size and pattern in the developing chick limb bud

Development ◽  
1981 ◽  
Vol 65 (Supplement) ◽  
pp. 129-150
Author(s):  
Dennis Summerbell

This paper examines the hypothesis that the developing chick limb bud has mechanisms for regulating the control of growth, size and pattern. The tests included: surgical removal of selected parts of the limb field, X-irradiation, temperature shock and the manipulation of known limb organizer regions (removal of the apical ectodermal ridge, or the addition of an extra zone of polarizing activity). The results strongly support the idea that there are regulatory mechanisms controlling both the pattern and the size of the limb and suggest that they involve regulation of the growth rate via control of cell division throughout the embryonic period. Possible mechanisms are discussed.

Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 219-226
Author(s):  
K. M. Bell ◽  
J. C. McLachlan

Two regions of the chick limb bud — the apical ectodermal ridge and the zone of polarizing activity — have been shown to influence cell division and pattern formation during normal development and following surgical manipulation. In this study, using a simple coculture system, together with autoradiography, we have shown that these morphogenetically active regions of the limb bud can stimulate quiescent 3T3 cells to initiate DNA synthesis to a significantly greater degree than comparable but morphogenetically inactive regions of the limb bud.


2003 ◽  
Vol 69 (2) ◽  
pp. 1287-1289 ◽  
Author(s):  
Mario Varcamonti ◽  
Maria R. Graziano ◽  
Romilde Pezzopane ◽  
Gino Naclerio ◽  
Slavica Arsenijevic ◽  
...  

ABSTRACT An insertional deoD mutant of Streptococcus thermophilus strain SFi39 had a reduced growth rate at 20°C and an enhanced survival capacity to heat shock compared to the wild type, indicating that the deoD product is involved in temperature shock adaptation. We report evidence that ppGpp is implicated in this dual response.


2020 ◽  
Author(s):  
Nolan K Maier ◽  
Jun Ma ◽  
Michael A Lampson ◽  
Iain M Cheeseman

SummaryTo generate haploid gametes, germ cells undergo two consecutive meiotic divisions requiring key changes to the cell division machinery. Here, we explore the regulatory mechanisms that differentially control meiotic events. We demonstrate that the protease Separase rewires key cell division processes at the meiosis I/II transition by cleaving the meiosis-specific protein Meikin. In contrast to cohesin, which is inactivated by Separase proteolysis, cleaved Meikin remains functional, but results in a distinct activity state. Full-length Meikin and the C-terminal Meikin Separase-cleavage product both localize to kinetochores, bind to Plk1 kinase, and promote Rec8 cleavage, but our results reveal distinct roles for these proteins in controlling meiosis. Mutations that prevent Meikin cleavage or that conditionally inactivate Meikin at anaphase I both result in defective meiosis II chromosome alignment. Thus, Separase cleavage of Meikin creates an irreversible molecular switch to rewire the cell division machinery at the meiosis I/II transition.


Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2711-2721 ◽  
Author(s):  
S. Qu ◽  
S.C. Tucker ◽  
J.S. Ehrlich ◽  
J.M. Levorse ◽  
L.A. Flaherty ◽  
...  

Mutations that affect vertebrate limb development provide insight into pattern formation, evolutionary biology and human birth defects. Patterning of the limb axes depends on several interacting signaling centers; one of these, the zone of polarizing activity (ZPA), comprises a group of mesenchymal cells along the posterior aspect of the limb bud that express sonic hedgehog (Shh) and plays a key role in patterning the anterior-posterior (AP) axis. The mechanisms by which the ZPA and Shh expression are confined to the posterior aspect of the limb bud mesenchyme are not well understood. The polydactylous mouse mutant Strong's luxoid (lst) exhibits an ectopic anterior ZPA and expression of Shh that results in the formation of extra anterior digits. Here we describe a new chlorambucil-induced deletion allele, lstAlb, that uncovers the lst locus. Integration of the lst genetic and physical maps suggested the mouse Aristaless-like4 (Alx4) gene, which encodes a paired-type homeodomain protein that plays a role in limb patterning, as a strong molecular candidate for the Strong's luxoid gene. In genetic crosses, the three lst mutant alleles fail to complement an Alx4 gene-targeted allele. Molecular and biochemical characterization of the three lst alleles reveal mutations of the Alx4 gene that result in loss of function. Alx4 haploinsufficiency and the importance of strain-specific modifiers leading to polydactyly are indicative of a critical threshold requirement for Alx4 in a genetic program operating to restrict polarizing activity and Shh expression in the anterior mesenchyme of the limb bud, and suggest that mutations in Alx4 may also underlie human polydactyly.


Development ◽  
1977 ◽  
Vol 40 (1) ◽  
pp. 1-21
Author(s):  
Dennis Summerbell

Removal of the apical ectodermal ridge causes a reduction in the rate of outgrowth of the wing-bud and the loss of distal parts. More specifically it causes a short-term increase in cell density and cell death and a decrease in the rate of cell proliferation. The evidence supports the hypothesis of density-dependent control of cell division and suggests that there may also be a mechanism regulating skeletal length at the time of differentiation. An informal model is presented to explain the observations.


Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
J.A. Helms ◽  
C.H. Kim ◽  
G. Eichele ◽  
C. Thaller

In the chick limb bud, the zone of polarizing activity controls limb patterning along the anteroposterior and proximodistal axes. Since retinoic acid can induce ectopic polarizing activity, we examined whether this molecule plays a role in the establishment of the endogenous zone of polarizing activity. Grafts of wing bud mesenchyme treated with physiologic doses of retinoic acid had weak polarizing activity but inclusion of a retinoic acid-exposed apical ectodermal ridge or of prospective wing bud ectoderm evoked strong polarizing activity. Likewise, polarizing activity of prospective wing mesenchyme was markedly enhanced by co-grafting either a retinoic acid-exposed apical ectodermal ridge or ectoderm from the wing region. This equivalence of ectoderm-mesenchyme interactions required for the establishment of polarizing activity in retinoic acid-treated wing buds and in prospective wing tissue, suggests a role of retinoic acid in the establishment of the zone of polarizing activity. We found that prospective wing bud tissue is a high-point of retinoic acid synthesis. Furthermore, retinoid receptor-specific antagonists blocked limb morphogenesis and down-regulated a polarizing signal, sonic hedgehog. Limb agenesis was reversed when antagonist-exposed wing buds were treated with retinoic acid. Our results demonstrate a role of retinoic acid in the establishment of the endogenous zone of polarizing activity.


Development ◽  
1972 ◽  
Vol 27 (1) ◽  
pp. 245-260
Author(s):  
D. A. Ede ◽  
O. P. Flint

Aggregates were prepared from dissociated mesenchyme cells obtained from normal and talpid mutant chick limb buds at stage 26 and were maintained for 4 days in culture. They were shown by autoradiographic techniques to consist initially of populations of unifoimly dedifferentiated cells within which chondrogenesis was initiated between 1 and 2 days, leading to the formation of areas of precartilage in the interior of the aggregates. Measurements of cell population density, cell death and cell division were made in precartilage and non-cartilage regions on sections prepared from normal and mutant aggregates fixed at 1-day intervals and were related to the pattern of chondrogenesis. Non-cartilage areas consisted of cells surrounding the precartilage areas and extended to the surface of the aggregate; these cells showed no special pattern or histochemical reaction. Precartilage areas consisted of one or more “;condensations”, comprising cells arranged in concentric rings around a central cell or group of cells, characterized by uptake of [35S]sulphate and taking up alcian blue stain in the intercellular matrix. Chondrogenesis was initiated al the condensation foci and spread centrifugally. Condensations were arranged in a simple pattern, roughly equidistantly from each other and never at the surface of the aggregate. The shape and arrangement of the cells comprising them suggested that they were formed by a process of aggregation towards the condensation foci. The relation of these observations to events in the intact limb bud developing in vivo is discussed.


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