Reduction of the rate of outgrowth, cell density, and cell division following removal of the apical ectodermal ridge of the chick limb-bud

Development ◽  
1977 ◽  
Vol 40 (1) ◽  
pp. 1-21
Author(s):  
Dennis Summerbell
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cell Division ◽  
Cell Density ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Short Term ◽  
Density Dependent ◽  
Wing Bud

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.

Posterior apical ectodermal ridge removal in the chick wing bud triggers a series of events resulting in defective anterior pattern formation

Development ◽  
1987 ◽  
Vol 101 (3) ◽  
pp. 501-515 ◽  
Author(s):  
W.L. Todt ◽  
J.F. Fallon
Keyword(s):  
Cell Death ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Direct Result ◽  
Posterior Border ◽  
Posterior Portion ◽  
Mesodermal Cell ◽  
Posterior Limb ◽  
Survival And Development ◽  
Wing Bud

The ability of the anterior apical ectodermal ridge to promote outgrowth in the chick wing bud when disconnected from posterior apical ridge was examined by rotating the posterior portion of the stage-19/20 to stage-21 wing bud around its anteroposterior axis. This permitted contact between the anterior and posterior mesoderm, without removing wing bud tissue. In a small but significant number of cases (10/54), anterior structures (digit 2) formed spatially isolated from posterior structures (digits 3 and 4). Thus, continuity with posterior ridge is not a prerequisite for anterior-ridge function in the wing bud. Nevertheless, posterior-ridge removal does result in anterior limb truncation. To investigate events leading to anterior truncation, we examined cell death patterns in the wing bud following posterior-ridge removal. We observed an abnormal area of necrosis along the posterior border of the wing bud at 6–12 h following posterior-ridge removal. This was followed by necrosis in the distal, anterior mesoderm at 48 h postoperatively and subsequent anterior truncation. Clearly, healthy posterior limb bud mesoderm is needed for anterior limb bud survival and development. We propose that anterior truncation is the direct result of anterior mesodermal cell death and that this may not be related to positional specification of anterior cells. In our view, cell death of anterior mesoderm, after posterior mesoderm removal, should not be used as evidence for a role in position specification by the polarizing zone during the limb bud stages of development. We suggest that the posterior mesoderm that maintains the anterior mesoderm need not be restricted to the mapped polarizing zone, but is more extensively distributed in the limb bud.

Myogenic cell movement in the developing avian limb bud in presence and absence of the apical ectodermal ridge (AER)

Development ◽  
1984 ◽  
Vol 80 (1) ◽  
pp. 105-125
Author(s):  
Madeleine Gumpel-Pinot ◽  
D. A. Ede ◽  
O. P. Flint
Keyword(s):  
Cell Migration ◽  
Cell Movement ◽  
Host Tissue ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Myogenic Cell ◽  
Myogenic Cells ◽  
Apical Direction ◽  
Wing Bud ◽  
Presence And Absence

Fragments of quail wing bud containing myogenic cells of somitic origin and fragments of quail sphlanchopleural tissue were introduced into the interior of the wing bud of fowl embryo hosts. No movement of graft into host tissue occurred in the control, but myogenic cells from the quail wing bud fragments underwent long migrations in an apical direction to become incorporated in the developing musculature of the host. When the apical ectodermal ridge (AER), together with some subridge mesenchyme, was removed at the time of grafting, no such cell migration occurred. The capacity of grafted myogenic cells to migrate in the presence of AER persists to H.H. stage 25, when myogenesis has begun, but premyogenic cells in the somites, which normally migrate out into the early limb bud, do not migrate when somite fragments are grafted into the wing bud. Coelomic grafts of apical and proximal wing fragments showed that apical sections of quail wing buds become invaded by myogenic cells of the host, but grafts from proximal wing bud regions do not.

A noble extended stochastic logistic model for cell proliferation with density-dependent parameters

2021 ◽  
Author(s):  
Trina Roy ◽  
Sinchan Ghosh ◽  
Bapi Saha ◽  
Sabyasachi Bhattacharya
Keyword(s):  
Cell Proliferation ◽  
Cell Density ◽  
Negative Feedback ◽  
Deterministic Model ◽  
Culture Media ◽  
Logistic Growth ◽  
Density Dependent ◽  
Proposed Model ◽  
Dependent Cell ◽  
Growth Inhibiting

Abstract Cell proliferation often experiences a density-dependent intrinsic proliferation rate (IPR) and negative feedback from growth-inhibiting molecules in culture media. The lack of flexible models with explanatory parameters fails to capture such a proliferation mechanism. We propose an extended logistic growth law with the density-dependent IPR and additional negative feedback. The extended parameters of the proposed model can be interpreted as density-dependent cell-cell cooperation and negative feedback on cell proliferation. Moreover, we incorporate further density regulation for flexibility in the model through environmental resistance on cells. The proposed growth law has similarities with the strong Allee model and harvesting phenomenon. We also develop the stochastic analog of the deterministic model by representing possible heterogeneity in growth-inhibiting molecules and environmental perturbation of the culture setup as correlated multiplicative and additive noises. The model provides a maximum sustainable stable cell density (MSSCD) and a new fitness measure for proliferative cells. The proposed model shows superiority to the logistic law after fitting to real cell culture datasets. We illustrate both MSSCD and the new cell fitness for a range of parameters. The cell density distributions reveal the chance of overproliferation, underproliferation, or decay for different parameter sets under the deterministic and stochastic setups.

Retinoic acid signaling is required during early chick limb development

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1385-1394 ◽  
Author(s):  
J.A. Helms ◽  
C.H. Kim ◽  
G. Eichele ◽  
C. Thaller
Keyword(s):  
Retinoic Acid ◽  
Limb Development ◽  
Acid Synthesis ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Retinoid Receptor ◽  
Limb Morphogenesis ◽  
Wing Bud ◽  
Zone Of Polarizing Activity

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.

Patterns of cell division, cell death and chondrogenesis in cultured aggregates of normal and talpid3 mutant chick limb mesenchyme cells

Development ◽  
1972 ◽  
Vol 27 (1) ◽  
pp. 245-260
Author(s):  
D. A. Ede ◽  
O. P. Flint
Keyword(s):  
Cell Death ◽  
Cell Division ◽  
Limb Bud ◽  
Intercellular Matrix ◽  
Blue Stain ◽  
Special Pattern ◽  
Mesenchyme Cells ◽  
Division Cell ◽  
Made In

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.

In vitro studies on the morphogenesis and differentiation of the mesoderm subjacent to the apical ectodermal ridge of the embryonic chick limb-bud

Development ◽  
1979 ◽  
Vol 50 (1) ◽  
pp. 75-97
Author(s):  
Robert A. Kosher ◽  
Mary P. Savage ◽  
Sai-Chung Chan
Keyword(s):  
Organ Culture ◽  
Chondrogenic Differentiation ◽  
Mesenchymal Cells ◽  
Apical Ectodermal Ridge ◽  
Limb Bud ◽  
Embryonic Chick ◽  
Marked Contrast ◽  
Culture Cells ◽  
Wing Bud

It has been suggested that one of the major functions of the apical ectodermal ridge (AER) of the embryonic chick limb-bud is to maintain mesenchymal cells directly subjacent to it (i.e. cells extending 00·4–00·5 mm from the AER) in a labile, undifferentiated condition. We have attempted to directly test this hypothesis by subjecting the undifferentiated subridgemesoderm of stage-25 embryonic chick wing-buds to organ culture in the presence and absence of the AER and the ectoderm that normally surrounds the mesoderm dorsally and ventrally. During the period of culture, control explants comprised of the subridge mesoderm capped by the AER and surrounded by the dorsal/ventral ectoderm undergo progressivemorphogenesis characterized by polarized proximal to distal outgrowth and changes in the contour of the developing explant, and ultimately form a structure grossly resembling a normal distal wing-bud tip. In contrast, explants from which the AER and dorsal/ventral ectoderm have been removed (minus ectoderm explants) or from which just the AER has been removed (minus AER explants) form compact, rounded masses exhibiting no signs of morphogenesis. During the polarized proximal to distal outgrowth control explants undergo during the first 3 days of culture, as cells of the explant become located greater than 0·4– 0·5 mm from the AER, they concomitantly undergo a sequence of changes indicative of their differentiation into cartilage. However, those cells which remain 0·4–0·5 mm from the AER during this period retain the characteristics of non-specialized mesenchymal cells. In marked contrast to control explants, virtually all of the cells of minus ectoderm explants initiate chondrogenic differentiation during the first day of culture. Cells comprising the central core of minus AER explants also initiate chondrogenic differentiation during the first day of culture, but in contrast to minus ectoderm explants, non-chondrogenic tissue types form along the periphery of the explants subjacent to the dorsal/ventral ectoderm. These results indicate that the AER maintains cells directly subjacent to it in a labile, undifferentiated condition, and that when mesenchymal cells are freed from the AER's influence either artificially or as a result of normal polarized outgrowth, they are freed to commence cytodifferentiation. The results further suggest that the dorsal/ventral ectoderm may have an influence on the differentiation of the mesenchymal cells directly subjacent to it, once the cells have been removed from the influence of the AER.

TRX-ASK1-JNK signaling regulation of cell density-dependent cytotoxicity in cigarette smoke-exposed human bronchial epithelial cells

2008 ◽  
Vol 294 (5) ◽  
pp. L921-L931 ◽  
Author(s):  
Yong Chan Lee ◽  
Chun-Yu Chuang ◽  
Pak-Kei Lee ◽  
Jin-Soo Lee ◽  
Richart W. Harper ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Cell Density ◽  
Cigarette Smoke ◽  
Airway Epithelium ◽  
Bronchial Epithelial Cells ◽  
Air Pollutant ◽  
Cigarette Smoke Exposure ◽  
Bronchial Epithelial ◽  
Density Dependent

Cigarette smoke is a major environmental air pollutant that injures airway epithelium and incites subsequent diseases including chronic obstructive pulmonary disease. The lesion that smoke induces in airway epithelium is still incompletely understood. Using a LIVE/DEAD cytotoxicity assay, we observed that subconfluent cultures of bronchial epithelial cells derived from both human and monkey airway tissues and an immortalized normal human bronchial epithelial cell line (HBE1) were more susceptible to injury by cigarette smoke extract (CSE) and by direct cigarette smoke exposure than cells in confluent cultures. Scraping confluent cultures also caused an enhanced cell injury predominately in the leading edge of the scraped confluent cultures by CSE. Cellular ATP levels in both subconfluent and confluent cultures were drastically reduced after CSE exposure. In contrast, GSH levels were significantly reduced only in subconfluent cultures exposed to smoke and not in confluent cultures. Western blot analysis demonstrated ERK activation in both confluent and subconfluent cultures after CSE. However, activation of apoptosis signal-regulating kinase 1 (ASK1), JNK, and p38 were demonstrated only in subconfluent cultures and not in confluent cultures after CSE. Using short interfering RNA (siRNA) to JNK1 and JNK2 and a JNK inhibitor, we attenuated CSE-mediated cell death in subconfluent cultures but not with an inhibitor of the p38 pathway. Using the tetracycline (Tet)-on inducible approach, overexpression of thioredoxin (TRX) attenuated CSE-mediated cell death and JNK activation in subconfluent cultures. These results suggest that the TRX-ASK1-JNK pathway may play a critical role in mediating cell density-dependent CSE cytotoxicity.

scholarly journals Cell proliferation and cell density of mesenchyme in the maxillary process and adjacent regions during facial development in the chick embryo

Development ◽  
1978 ◽  
Vol 46 (1) ◽  
pp. 65-74
Author(s):  
Robert Minkoff ◽  
Amy J. Kuntz
Keyword(s):  
Cell Proliferation ◽  
Cell Density ◽  
Regulatory Mechanism ◽  
Satisfactory Explanation ◽  
Density Dependent ◽  
Dna Labeling ◽  
Inhibition Of Growth ◽  
Developmental Age ◽  
Dependent Inhibition ◽  
Facial Development

Cell proliferation, as measured by DNA labeling indices was analyzed during the early development of the maxillary process. Chick embryos were labeled with [3H]thymidine for .1 h and processed for autoradiography. The percentage of labeled mesenchymal cells was determined within delineated areas in the maxillary processes and in adjacent regions. Analysis of labeling indices in each of the areas at successive stages of development demonstrated a pattern of declining rates of cell proliferation with advancing developmental age. Cell proliferation in adjacent regions declined earlier and, in some instances, faster than it did in the maxillary process. Cell density was measured in the maxillary process and the roof of the stomodeum and was found to be higher in the maxillary process throughout the period studied. Cell density and cell proliferation data were analyzed with reference to the operation of ‘density-dependent inhibition’ of growth as a regulatory mechanism for the observed changes. ‘Density-dependent inhibition’ of growth was not a satisfactory explanation for the observed differences between the maxillary process and adjacent regions.

Development of the apical ectodermal ridge in the chick wing bud

Development ◽  
1984 ◽  
Vol 80 (1) ◽  
pp. 21-41
Author(s):  
John F. Fallon ◽  
William L. Todt
Keyword(s):  
Cell Death ◽  
Histological Examination ◽  
Late Stage ◽  
Apical Ectodermal Ridge ◽  
Columnar Epithelium ◽  
Anteroposterior Axis ◽  
Wing Bud ◽  
Temporal Location

Histological examination of the stage-18 to stage-23 chick wing bud apex revealed the following. Initially, the wing bud was covered by a cuboidal to columnar epithelium with an overlying periderm. Thickening of the apical ectoderm was not obvious until late stage 18 (36 pairs of somites), after the appearance of the wing bud. At late stage 18, cells of the inner layer of ectoderm had elongated slightly along an axis perpendicular to the epithelial-mesenchymal interface. Well-defined apical ectodermal ridge morphology, i.e., pseudostratified columnar epithelium with an overlying periderm, was not apparent until stage 20. Subsequently the ridge lengthened along the anteroposterior perimeter of the wingbud. We demonstrated histologically that the apical ectodermal ridge of the wing bud was asymmetric with respect to the anteroposterior axis, in that there was more ridge associated with posterior mesoderm. Other observations include the spatial and temporal location of a groove in the base of the thickest part of the ridge. The groove can be correlated with the specification of distal wing elements. The groove was first seen at stage 20 and became more prominent through stage 23. An anteroposterior progression of ectodermal cell death was also observed. This began at late stage 18 and continued through each of the stages examined.

Effects of Mechanical Vibration on Proliferation and Differentiation of Neural Stem Cells

2008 ◽  
Author(s):  
Kei Suzuki ◽  
Toshihiko Shiraishi ◽  
Shin Morishita ◽  
Hiroshi Kanno
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cell Division ◽  
Neural Stem Cells ◽  
Cell Density ◽  
Mechanical Vibration ◽  
Nerve Cells ◽  
Cell Marker ◽  
Glia Cells

Neural stem cells have been studied to promote neurogenesis in regenerative therapy. The control of differentiation of neural stem cells to nerve cells and the increase of the number of nerve cells are needed. For the purpose of them, it is important to investigate not only chemical factors but also mechanical factors such as hydrostatic pressure in brain and mechanical vibration in walking. In this study, sinusoidal inertia force was applied to cultured neural stem cells and the effects of mechanical vibration on the cells were investigated. After the cells were cultured in culture plates for one day and adhered on the cultured plane, vibrating group of the culture plates was set on an aluminum plate attached to an exciter and cultured under sinusoidal excitation for 24 hours a day during 26 days. The amplitude of the acceleration on the culture plate was set to 0.25 G and the frequency was set to 25 Hz. The time evolution of cell density was obtained by counting the number of cells at every 3 or 4 days. The expression of Akt, phosphorylated Akt (p-Akt), MAPK, and phosphorylated MAPK (p-MAPK) was detected by western blotting analysis at 7 days of culture to understand the mechanism of cell proliferation. Akt and MAPK are part of signaling pathways in relation to cell proliferation. The phosphorylation of Akt suppresses apoptosis and the phosphorylation of MAPK activates cell division. The gene expression of MAP-2, NFH, GFAP, and nestin was detected by real-time RT-PCR analysis at 7 days of culture to obtain a ratio of differentiation of neural stem cells to nerve or glia cells. MAP-2 and NFH are nerve cell markers, GFAP is a glia cell marker, and nestin is a stem cell marker. The results obtained are as follows. The cell density of the vibrating group was three times higher than that of the non-vibrating group at 26 days of culture. p-Akt was enhanced by the mechanical vibration while p-MAPK was not. There is no significant difference of the gene expression level of MAP-2, NFH, GFAP, and nestin between the vibrating and non-vibrating groups. These results suggest that the mechanical vibration promotes the proliferation of neural stem cells and its cause is likely the suppression of apoptosis but not the activation of cell division, and that the mechanical vibration at the experimental condition does not affect the differentiation of neural stem cells to nerve or glia cells.

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