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A García-Bellido

Publications and source records attributed to A García-Bellido.

At least 19 recordsLinked to original sources
PubMed2001

Germ cell selection in genetic mosaics in Drosophila melanogaster.

Heritable mutations in the germ line lead to genetically heterogeneous, or mosaic, gonads. Many of the genes used in germ-line development also play roles in somatic development [Saffman, E. E. & Lasko, P. (1999) Cell. Mol. Life Sci. 55, 1141-1163]. Mutations in these genes may have cellular phenotypes throughout germ-line development leading to their differential elimination or survival, as has been observed in somatic cells [Morata, G. & Ripoll, P. (1975) Dev. Biol. 42, 211-221]. We investigate whether mutations in heterozygosis are subject to pregametic selection in the germ line. We initiated clones of wild-type homozygous cells at different stages of development in gonads heterozygous for eight different recessive chromosome deficiencies. Here we show that cell selection takes place in mosaic germ-line populations. This phenomenon represents a level of selection that precedes and conditions subsequent zygotic selection by affecting the genes available in the gametic population.

Animals↗
PubMed2000

Cell behaviour of Drosophila fat cadherin mutations in wing development.

We have studied several cell behaviour parameters of mutant alleles of fat (ft) in Drosophila imaginal wing disc development. Mutant imaginal discs continue growing in larvae delayed in pupariation and can reach sizes of several times those of wild-type. Their growth is, however, basically allometric. Homozygous ft cells grow faster than their twin cells in clones and generate larger territories, albeit delimited by normal clonal restrictions. Moreover, ft cells in clones tend to grow towards wing proximal regions. These behaviours can be related with failures in cell adhesiveness and cell recognition. Double mutant combinations with alleles of other genes, e.g. of the Epidermal growth factor receptor (DER) pathway, modify ft clonal phenotypes, indicating that adhesiveness is modulated by intercellular signalling. Mutant ft cells show, in addition, smaller cell sizes during proliferation and abnormal cuticular differentiation, which reflect cell membrane and cytoskeleton anomalies, which are not modulated by the DER pathway.

Alleles↗
PubMed2000

Relationships between extramacrochaetae and Notch signalling in Drosophila wing development.

The function of extramacrochaetae is required during the development of the Drosophila wing in processes such as cell proliferation and vein differentiation. extramacrochaetae encodes a transcription factor of the HLH family, but unlike other members of this family, Extramacrochaetae lacks the basic region that is involved in interaction with DNA. Some phenotypes caused by extramacrochaetae in the wing are similar to those observed when Notch signalling is compromised. Furthermore, maximal levels of extramacrochaetae expression in the wing disc are restricted to places where Notch activity is higher, suggesting that extramacrochaetae could mediate some aspects of Notch signalling during wing development. We have studied the relationships between extramacrochaetae and Notch in wing development, with emphasis on the processes of vein formation and cell proliferation. We observe strong genetic interaction between extramacrochaetae and different components of the Notch signalling pathway, suggesting a functional relationship between them. We show that the higher level of extramacrochaetae expression coincides with the domain of expression of Notch and its downstream gene Enhancer of split-m(beta). The expression of extramacrochaetae at the dorso/ventral boundary and in boundary cells between veins and interveins depends on Notch activity. We propose that at least during vein differentiation and wing margin formation, extramacrochaetae is regulated by Notch and collaborates with other Notch-downstream genes such as Enhancer of split-m(beta).

Animals↗
PubMed1999

Dual role of extramacrochaetae in cell proliferation and cell differentiation during wing morphogenesis in Drosophila.

The Extramacrochaetae (emc) gene encodes a transcription factor with an HLH domain without the basic region involved in interaction with DNA present in other proteins that have this domain. EMC forms heterodimers with bHLH proteins preventing their binding to DNA, acting as a negative regulator. The function of emc is required in many developmental processes during the development of Drosophila, including wing morphogenesis. Mitotic recombination clones of both null and gain-of-function alleles of emc, indicate that during wing morphogenesis, emc participates in cell proliferation within the intervein regions (vein patterning), as well as in vein differentiation. The study of relationships between emc and different genes involved in wing development reveal strong genetic interactions with genes of the Ras signalling pathway (torpedo, vein, veinlet and Gap), blistered, plexus and net, in both adult wing phenotypes and cell behaviour in genetic mosaics. These interactions are also analyzed as variations of emc expression patterns in mutant backgrounds for these genes. In addition, cell proliferation behaviour of emc mutant cells varies depending on the mutant background. The results show that genes of the Ras signalling pathway are co-operatively involved in the activity of emc during cell proliferation, and later antagonistically during cell differentiation, repressing EMC expression.

Alleles↗
PubMed1998

The relative expression amounts of apterous and its co-factor dLdb/Chip are critical for dorso-ventral compartmentalization in the Drosophila wing.

Dorso-ventral axis formation in the Drosophila wing requires the localized accumulation of the Apterous LIM/homeodomain protein (Ap) in dorsal cells. Here we report that dLdb/Chip encodes a LIM-binding cofactor that controls Ap activity. Both lack and excess of dLdb/Chip function cause the same phenotype as apterous (ap) lack of function; i.e. dorsal to ventral transformations, generation of new wing margins, and wing outgrowths. These results indicate that the normal function of Ap in dorso-ventral compartmentalization requires the correct amount of the DLDB/CHIP co-factor, and suggest that the Ap and DLDB/CHIP proteins form a multimeric functional complex. In support of this model, we show that the dLdb/Chip excess-of-function phenotypes can be rescued by ap overexpression.

Animals↗
PubMed1998

Two-dimensional gel analysis of proteins in the Drosophila wing imaginal disc mutants fat and lethal (2) giant discs.

High-resolution two-dimensional (2D) gel electrophoresis coupled with computer analysis has been used to construct a quantitative protein database of Drosophila mature wing imaginal discs. The level of expression for all of the detected proteins has been quantitatively determined. This database has been used to evaluate changes in the patterns of protein synthesis in wing imaginal discs from two Drosophila melanogaster mutants with abnormal wing disc development: fat (ft) and two different alleles of lethal (2) giant disc (l(2)gd). Patterns of pulse-labeled proteins of the different mutants show variations in both qualitative and quantitative parameters of synthesis. In this comparison we have detected specific sets of protein changes characteristic of both alleles of the same locus and a set of protein changes common to both loci. How the abnormal expression of these proteins relates to the abnormal process of mutant hyperplasia is discussed.

Animals↗
PubMed1998

Screening of larval/pupal P-element induced lethals on the second chromosome in Drosophila melanogaster: clonal analysis and morphology of imaginal discs.

We have carried out screens for lethal mutations on the second chromosome of Drosophila melanogaster that are associated with abnormal imaginal disc morphologies, particularly in the wing disc. From a collection of 164 P element-induced mutations with a late larva/pupa lethal phase we have identified 56 new loci whose gene products are required for normal wing disc development and for normal morphology of other larval organs. Genetic mosaics of these 56 mutant lines show clonal mutant phenotypes for 23 cell-viable mutations. These phenotypes result from altered cell parameters. Causal relationships between disc and clonal phenotypes are discussed.

Animals↗
PubMed1998

Genetic interactions and cell behaviour in blistered mutants during proliferation and differentiation of the Drosophila wing.

In this work, we analyse the blistered function in wing vein development by studying genetic mosaics of mutant cells, genetic interactions with other genes affecting vein development and blistered expression in several mutant backgrounds. blistered encodes for a nuclear protein homologous to the mammalian Serum Response Factor and is expressed in presumptive intervein cells of third larval instar and pupal wing discs. Clones of blistered mutant cells proliferate normally but tend to grow along veins and always differentiate as vein tissue. These observations indicate that vein-determined wing cells show a particular behaviour that is responsible for their allocation to vein regions. We observe strong genetic interactions between blistered, veinlet and genes of the Ras signaling cascade. During disc proliferation, blistered expression is under the control of the Ras signal transduction pathway, but its expression is independent of veinlet. During the pupal period, blistered and veinlet expression become interdependent and mutually exclusive. These results link the activity of the Ras pathway to the process of early determination of intervein cells, by the transcriptional control of the blistered nuclear factor.

Animals↗
PubMed1998

Cell proliferation in the attainment of constant sizes and shapes: the Entelechia model.

The Entelechia model is a generative model of morphogenesis where individual cells exhibit surface labels that express scalar difference and planar polarity along two orthogonal axes X and Y. The amount of surface label depends on the level of Martial (M) gene product within each cell. The model assumes that the confrontation of cells on both sides of compartment borders causes an increase in their level of M gene expression. The resulting disparity between the M value of border cells and that of their neighbors induces the latter to divide. After each division the daughter cells increase their own M value, and allocate to the best matching value position. The increase in M value at the borders therefore extends through the anlage in a cascade of proliferation. The Entelechia condition is reached when the border cells attain the species-specific maximal M values, and the value differences between adjacent cells become indistinguishable. Computer simulations reveal that this model accounts for a variety of observations made on imaginal discs, e.g., 1) each disc attains a constant size in terms of number of cells, independently of the growing conditions; 2) clonal restrictions separate populations of cells which proliferate by intercalar growth; 3) dissociated cells are capable of reconstructing original patterns upon reaggregation, and 4) genetic mosaics of morphogenetic mutations show local effects that may differ depending on the position of the mutant cells in the growing anlage.

Algorithms↗
PubMed1998

Debatable issues. Interview by Alain Ghysen..

This paper reports a discussion between Antonio Garcia-Bellido and Lewis Wolpert about a number of questions raised by Alain Ghysen. The questions follow, in reverse order, the subjects dealt with in this issue: first the principles (are there unifying principles of development?), then questions dealing with evolution (why are patterns conserved?) and with the homeotic genes (what is their function?), then the cell biology of development (who is controlling actual morphogenesis?), and the generation and evolution of patterns (what makes development so reproducible and how does it change from one species to another?) and finally about the genetics of cell determination and specification (how does a cell measure its position?). Obviously the discussion did not provide any firm answers to any of these questions. Perhaps more importantly, it provides a vivid picture of two contrasting ways of thinking about developmental problems.

Animals↗
PubMed1997

Proximo-distal specification in the wing disc of Drosophila by the nubbin gene.

Mutations in the nubbin (nub) gene have a phenotype consisting of a severe wing size reduction and pattern alterations, such as transformations of distal elements into proximal ones. nub expression is restricted to the wing pouch cells in wing discs since early larval development. These effects are also observed in genetic mosaics where cell proliferation is reduced in all wing blade regions autonomously, and transformation into proximal elements is observed in distal clones. Clones located in the proximal region of the wing blade cause in addition nonautonomous reduction of the whole wing. Cell lineage experiments in a nub mutant background show that clones respect neither the anterior-posterior nor the dorsal-ventral boundary but that the selector genes have been correctly expressed since early larval development. The phenotypes of nub el and nub dpp genetic combinations are synergistic and the overexpression of dpp in clones in nub wings does not result in overproliferation of the surrounding wild-type cells. We discuss the role of nub in the wing's proximo-distal axis and in the formation of compartment boundaries.

Animals↗
PubMed1997

Developmental parameters of cell death in the wing disc of Drosophila.

Apoptotic cell death in wing imaginal discs takes place in single cells or small clusters of neighboring cells. These cells are distributed throughout the anlage at early stages and in recognizable territories at late larval and pupal stages. Apoptotic cells remain in the epithelium 2-4 h, prior to being engulfed in place by hemolymph cells. Experimentally induced apoptosis in single cells or territories is accompanied by nonautonomous death of adjacent cells and of cells further away in adjacent territories. These effects are followed by changes in cell proliferation in both territories. Apogenetic mosaics in mutant discs show cell death throughout the anlage. Apoptosis provides a mechanism, in addition to cell proliferation control, for matching territories with different positional values or different genetic specifications.

Animals↗
PubMed1997

Wing surface interactions in venation patterning in Drosophila.

The adult wing of Drosophila consists of two wing surfaces apposed by their basal membranes which first came into contact following disc eversion at metamorphosis. Veins appear in these surfaces in a dorsal-ventral symmetric pattern, but are 'corrugated' (vein cells are more compacted and more pigmented) in a dorsal-ventral asymmetric pattern. We prevented dorsal-ventral contact apposition during wing imaginal disc morphogenesis by implanting fragments of discs into metamorphosing hosts. In these implants, longitudinal veins differentiate but with wider corrugation and in both surfaces. These results and those of genetic mosaics of mutants removing veins or causing ectopic veins reveal mutual dorso-ventral induction/inhibition at work to modulate the final vein differentiation pattern and corrugation.

Animals↗
PubMed1996

Symmetries throughout organic evolution.

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.

Evolution, Molecular↗
PubMed1996

Cell cycling and patterned cell proliferation in the Drosophila wing during metamorphosis.

In metamorphosing wing discs, progression through the cell cycle takes place, as in larval discs, in nonclonally derived clusters of cells synchronized in the same cell cycle stage. Contrary to early discs, there are temporal and spatial heterogeneities in cell proliferation associated with wing margin, vein, intervein, and middle intervein territories. Within these territories, there are no indications of a wave progression of the cell cycle. Mitotic orientations are, as in early discs, at random but there is a preferential allocation of postmitotic cells along the proximodistal axis, thus explaining the elongated shape of the resulting clones along this axis. Shapes of clones in mature discs and in evaginated wings are similar, thus excluding major morphogenetic movements during evagination. After the proliferative period, all the cells are arrested in G1 phase. The final number of cells of the wing is fixed independently of experimental perturbations that alter the cell division schedule. These results are discussed in the context of a model of wing morphogenesis.

Animals↗
PubMed1996

Mutations in the rotated abdomen locus affect muscle development and reveal an intrinsic asymmetry in Drosophila.

In bilateral animals, the left and right sides of the body usually present asymmetric structures, the genetic bases of whose generation are still largely unknown [CIBA Foundation (1991) Biological Asymmetry and Handedness, CIBA Foundation Symposium 162 (Wiley, New York), pp. 1-327]. In Drosophila melanogaster, mutations in the rotated abdomen (rt) locus cause a clockwise helical rotation of the body. Even null alleles are viable but exhibit defects in embryonic muscle development, rotation of the whole larval body, and helical staggering of cuticular patterns in abdominal segments of the adult. rotated abdomen is expressed in the embryonic mesoderm and midgut but not in the ectoderm; it encodes a putative integral membrane glycoprotein (homologous to key yeast mannosyltransferases). Mesodermal cells defective in O-glycosylation lead to an impaired larval muscular system. We propose that the staggering of the adult abdominal segments would be a consequence of the relaxation of intrinsic rotational torque of muscle architecture, preventing the colateral alignment of the segmental histoblast cells during their proliferation at metamorphosis.

Amino Acid Sequence↗
PubMed1996

Cell cycling and patterned cell proliferation in the wing primordium of Drosophila.

The pattern of cell proliferation in the Drosophila imaginal wing primordium is spatially and temporally heterogeneous. Direct visualization of cells in S, G2, and mitosis phases of the cell cycle reveals several features invariant throughout development. The fraction of cells in the disc in the different cell cycle stages is constant, the majority remaining in G1. Cells in the different phases of the cell cycle mainly appear in small synchronic clusters that are nonclonally derived but result from changing local cell-cell interactions. Cluster synchronization occurs before S and in the G2/M phases. Rates of cell division are neither constant nor clonal features. Cell cycle progression is linear rather than concentric. Clusters appear throughout the disc but with symmetries related to presumptive wing patterns, compartment boundaries, and vein clonal restrictions.

Animals↗