Symmetries throughout Organic Evolution Garcia-Bellido, Antonio
Proceedings of the National Academy of Sciences - PNAS,
12/1996, Letnik:
93, Številka:
25
Journal Article
Recenzirano
Odprti dostop
The biological realm has inherited symmetries from the physicochemical realm, but with the increasing complexity at higher phenomenological levels of life, some inherited symmetries are broken while ...novel symmetries appear. These symmetries are of two types, structural and operational. Biological novelties result from breaking operational symmetries. They are followed by acquisition of regularity and stability, in a recurrent process throughout complexity levels.
The Drosophila homologue of the epidermal growth factor receptor (DEGFr or DER, also called torpedo or top) has many mutant alleles that cause either embryonic lethality (both early and late), pupal ...lethality or female sterility, possibly corresponding to degrees of hypomorphism. We have studied the clonal behaviour of some lethal alleles in genetic mosaics in the imaginal development of thorax, head and tergite epidermis. These alleles cause reduced cell viability to different degrees (measured in frequency and size of clones), smaller cell sizes, abnormal patterning of sensory-organ differentiation and lack of differentiation of macro-chaetae and veins. These effects are cellautonomous but also cause abnormal differentiation in wild-type cells surrounding the clones. In addition, we have studied the phenotypes of double mutant combinations of viable top alleles with wingpattern mutants, some related to other Drosophila proto-oncogenes, to reveal gene interactions in the role(s) of DER in cell proliferation and differentiation. We discuss how those complex cell-behaviour phenotypes and genetic interactions are related to the molecular nature of the DER.
Drosophila imaginal discs are monolayered epithelial invaginations that grow during larval stages and evert at metamorphosis to assemble the adult exoskeleton. They consist of columnar cells, forming ...the imaginal epithelium, as well as squamous cells, which constitute the peripodial epithelium and stalk (PS). Here, we uncover a new morphogenetic/cellular mechanism for disc eversion. We show that imaginal discs evert by apposing their peripodial side to the larval epidermis and through the invasion of the larval epidermis by PS cells, which undergo a pseudo-epithelial-mesenchymal transition (PEMT). As a consequence, the PS/larval bilayer is perforated and the imaginal epithelia protrude, a process reminiscent of other developmental events, such as epithelial perforation in chordates. When eversion is completed, PS cells localize to the leading front, heading disc expansion. We found that the JNK pathway is necessary for PS/larval cells apposition, the PEMT, and the motile activity of leading front cells.
Abstract Background aims In this report, we describe the successful bronchoscopic management of bronchopleural fistula in two patients, using autologous adipose-derived stromal cells. Cell therapy ...was considered for 2 cases of bronchopleural fistula refractory to conventional surgical treatment after control of the primary disease was confirmed and active pleural infection was ruled out. Briefly, adipose-derived stem cells were first isolated from lipoaspirate and used without cell expansion. In 24 months, we have not received more patients with bronchopleural fistula in our hospital and we have not been able to include more patients. Methods Briefly, adipose-derived stem cells were first isolated from lipo-aspirate and used without cell expansion. A bronchopleural fistula was identified through bronchoscopy, and the mucosa surrounding the fistula was ablated with an argon plasma coagulator. Isolated stem cells were then endoscopically injected into the de-epithelialized area and fistulous tract. If an open thoracostomy was present at the time of the intervention, the same procedure was performed on the pleural side. Bronchoscopic follow-up was scheduled weekly during the first month, monthly during the first year, and then yearly. The underlying etiologies were left pneumonectomy and right lower video-assisted lobectomy for non–small-cell lung cancer. The sizes of the fistulas were 6 mm and 3 mm in diameter, respectively. Results Both patients were discharged on the first postoperative day. The 3-year follow-up revealed a successful and maintained fistula closure, no treatment-related adverse reactions, nonlocal malignant recurrence and improved quality of life. Conclusions This preliminary study showed that bronchoscopic application of autologous adipose-derived stem cells is a feasible, safe and effective procedure for treating bronchopleural fistula.
This paper proposes a parallel evolutionary algorithm to tackle the fully interconnected network design problem (FINDP), a specific application of hub location to network design. The FINDP has been ...recently proposed as an NP-hard combinatorial optimization problem formed by two smaller sub-problems: first, given the nodes which form the network, classify them as belonging to the backbone network or not. The second sub-problem consists of assigning the access network to a hub (node of the backbone network). In this paper we propose a parallel evolutionary algorithm to tackle the FINDP. We describe the architecture and how to structure the algorithm to solve the problem. Experimental tests have been carried out in several synthetic instances, and a comparison with existing approaches have shown the good performance of our algorithm.
The polarity mutants pk, sple, mwh, fz and in alter the orientations of cuticular processes in several regions of the body. The mutant polarity patterns are constant and do not result from ...alterations in cell lineage. Polarity patterns are locus specific rather than allele specific (new alleles express the same polarity patterns as the original alleles). In the wing, polarity formation is largely cell autonomous and is independent of the anteroposterior compartment boundary. By genetic and physiological manipulation it is shown that the mutant polarity patterns are unaffected by the size of the wing blade or the number of cells that form it. Mutants which remove parts of the wing margin or alter the distribution pattern of wing veins do not alter the mutant polarity patterns. Thus, neither the wing margins nor the pattern of vein tissue act as spatial references for polarity formation. The determination of mutant polarity patterns is not dependent on the overall topology of the wing blade but is region-specific. The mutants affect several independent functions. The possible wild-type function of the loci in polarity formation is discussed.
The Drosophila Notch gene product is a transmembrane protein that functions as a receptor of intercellular signals in several Drosophila developmental processes. Two other transmembrane proteins, ...encoded by the genes Delta and Serrate, genetically and molecularly behave as Notch ligands. All these proteins share the presence of epidermal growth factor (EGF)-like repeats in their extracellular domain. The Notch protein has 36 EGF-like repeats, 2 of which, numbers 11 and 12, are required for the interaction with the Delta and Serrate ligands. We have isolated and molecularly characterized a Notch mutation in its Delta- and Serrate-binding domain that behaves genetically as both a Notch antimorphic and a loss-of-function mutation. This mutation, NM1, carries a Glu leads to Val substitution in the Notch EGF repeat 12. The NM1 allele interacts with other Notch alleles such as Abruptex and split and with mutations in the Notch-ligand genes Delta and Serrate. The basis for the genetic antimorphism of NM1 seems to reside in the titration of Notch wild-type products into NM1/N+ nonfunctional dimers and/or the titration of Delta products into nonfunctional ligand-receptor complexes
The present work is a detailed analysis of the numerical and positional parameters of cell proliferation in all of the derivatives of the wing disk. We have made use of twin clones resulting from ...mitotic recombination events at three different ages of development. The interfaces between twin clones indicate the relative position in the anlage of the mother cells. Interface types vary with age of clone initiation and with wing regions. They are indicative of the main allocation of postmitotic cells of the growing clones. Growth is exponential and intercalar, i.e., the progeny of ancestor cells becomes more and more separated. Clones are compact, indicating that daughter cells tend to remain side by side. The shape of the clones is wing region characteristic. Subpopulations of cells grow preferentially along veins and wing margins and show characteristic shapes in different pleural regions. The shape and size of the adult wing regions largely depend on the shape of clones and hence of the allocation of successive rounds of daughter cells. The role of mitogenic morphogens in wing size and shape is discussed.
Most carcinomas present some form of chromosome instability in combination with spindle defects. Numerical instability is likely caused by spindle aberrations, but the origin of breaks and ...translocations remains elusive. To determine whether one mechanism can bring about both types of instability, we studied the relationship between DNA damage and spindle defects. Although lacking apparent repair defects, primary Dido mutant cells formed micronuclei containing damaged DNA. The presence of centromeres showed that micronuclei were caused by spindle defects, and cell cycle markers showed that DNA damage was generated during mitosis. Although the micronuclei themselves persisted, the DNA damage within was repaired during S and G2 phases. DNA breaks in Dido mutant cells regularly colocalized with centromeres, which were occasionally distorted. Comparable defects were found in APC mutant cell lines, an independent system for spindle defects. On the basis of these results, we propose a model for break formation in which spindle defects lead to centromere shearing.
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