PubMed Health⌕ Search

Biomedical subjects

A Martinez Arias

Publications and source records attributed to A Martinez Arias.

17 recordsLinked to original sources
PubMed2001

Wnt signalling: a theme with nuclear variations.

Wnt proteins are involved in a large number of events during development and disease. The crucial element in the transduction of the signal elicited by Wnt is the state and activity of beta-catenin. There are two pools of beta-catenin, one associated with cadherins at the cell surface and a soluble one in the cytolasm, whose state and concentration are critical for Wnt signalling. In the absence of Wnt, the cytoplasmic pool is low due to targetted degradation of beta-catenin. Upon Wnt signalling, beta-catenin is stabilized. As a consequence, it can access the nucleus where it interacts with members of the Tcf family of transcription factors to modulate the expression of defined targets. Recent reports indicate that, in addition to Tcfs, beta-catenin can interact with other nuclear proteins raising the possibility that Wnt signalling has a wider modulatory effect on transcription than is mediated by its interactions with Tcfs. BioEssays 23:311-318, 2001.

Animals↗
PubMed2000

The informational content of gradients of Wnt proteins.

This perspective tackles the issues facing developmental biologists and cell biologists regarding how the molecular mechanisms for specifying cell fate are defined. This perspective focuses on members of the Wnt family. The author proposes that Wnt proteins may act as stabilizing signals for earlier inductive events in certain systems, for example, in Caenorhabditis elegans during the migration of two neurons and in Drosophila melanogaster during the patterning of the wing.

Animals↗
PubMed2000

Structural requirements for notch signalling with delta and serrate during the development and patterning of the wing disc of Drosophila.

The delta and Serrate proteins interact with the extracellular domain of the Notch receptor and initiate signalling through the receptor. The two ligands are very similar in structure and have been shown to be interchangeable experimentally; however, loss of function analysis indicates that they have different functions during development and analysis of their signalling during wing development indicates that the Fringe protein can discriminate between the two ligands. This raises the possibility that the signalling of delta and Serrate through Notch requires different domains of the Notch protein. Here we have tested this possibility by examining the ability of delta and Serrate to interact and signal with Notch molecules in which different domains had been deleted. This analysis has shown that EGF-like repeats 11 and 12, the RAM-23 and cdc10/ankyrin repeats and the region C-terminal to the cdc10/ankyrin repeats of Notch are necessary for both delta and Serrate to signal via Notch. They also indicate, however, that delta and Serrate utilise EGF-like repeats 24-26 of Notch for signalling, but there are significant differences in the way they utilise these repeats.

Amino Acid Sequence↗
PubMed2000

Two different activities of Suppressor of Hairless during wing development in Drosophila.

The Notch pathway plays a crucial and universal role in the assignation of cell fates during development. In Drosophila, Notch is a transmembrane protein that acts as a receptor of two ligands Serrate and delta. The current model of Notch signal transduction proposes that Notch is activated upon binding its ligands and that this leads to the cleavage and release of its intracellular domain (also called Nintra). Nintra translocates to the nucleus where it forms a dimeric transcription activator with the Su(H) protein. In contrast with this activation model, experiments with the vertebrate homologue of Su(H), CBF1, suggest that, in vertebrates, Nintra converts CBF1 from a repressor into an activator. Here we have assessed the role of Su(H) in Notch signalling during the development of the wing of Drosophila. Our results show that, during this process, Su(H) can activate the expression of some Notch target genes and that it can do so without the activation of the Notch pathway or the presence of Nintra. In contrast, the activation of other Notch target genes requires both Su(H) and Nintra, and, in the absence of Nintra, Su(H) acts as a repressor. We also find that the Hairless protein interacts with Notch signalling during wing development and inhibits the activity of Su(H). Our results suggest that, in Drosophila, the activation of Su(H) by Notch involve the release of Su(H) from an inhibitory complex, which contains the Hairless protein. After its release Su(H) can activate gene expression in absence of Nintra.

Animals↗
PubMed1998

Wing development and specification of dorsal cell fates in the absence of apterous in Drosophila.

The development and patterning of the Drosophila wing relies on interactions between cell populations that have the anteroposterior (AP) axis and dorsoventral (DV) axis of the wing imaginal disc as frames of reference [1-3]. Each of these cell populations gives rise to a compartment - a group of cells that have their fates restricted by cell lineage - within which cells acquire specific identities through the expression of 'selector' genes [1,2,4]. The genes engrailed (en) and invected (inv), for example, label cells in the posterior compartment and mediate a set of cell interactions that direct the patterning and growth of the wing along the AP axis [1,2,4]. A similar situation has been proposed to exist across the DV axis, along with apterous (ap) as a dorsal selector gene [5], mediating cell interactions by regulating the expression of Serrate (Ser) [6] [7] and fringe (fng) [8]. In ap mutants, the wing is lost [5] [9], and here we report that this phenotype can be rescued by ectopic expression of either Ser or fng and that, surprisingly, the resulting wings have both dorsal and ventral cell fates.

Animals↗
PubMed1998

Interactions between Wingless and Notch during the assignment of cell fates in Drosophila.

A large number of observations suggest that, during Drosophila development there are close functional interactions between the activity of Notch receptor and that of a signaling molecule encoded by wingless gene. In this essay, I summarize these interactions and discuss the possibility that Wingless acts as a ligand for Notch as part of a switch that is iteratively involved in the assignation of cell fates during development.

Animals↗
PubMed1995

Serrate and wingless cooperate to induce vestigial gene expression and wing formation in Drosophila.

BACKGROUND: The appendages of insects, like the limbs of vertebrates, grow out of the body wall after the establishment of a proximo-distal axis among a group of primordial cells. In Drosophila, the wing develops in the limbless larva from one of the imaginal discs of the thorax, which give rise to the adult epidermis. The earliest identified requirement in wing development is for the induction of vestigial (vg) gene expression at the interface between ventral cells and dorsal cells of the wing disc. It has been proposed that this event requires two reciprocal signals--one from the dorsal to the ventral cells and the other from the ventral to the dorsal cells--which trigger vg expression at the presumptive wing margin and hence initiate the development of the wing tissue. RESULTS: We have identified four genes--Serrate (Ser), wingless (wg), Notch and Suppressor of Hairless (Su(H))--whose activity is required during the second and early third larval instars for the expression of vg. Analysis of the functions and patterns of expression of these genes at the time of the inductive event indicates that the Ser protein acts as a dorsal signal, and the Wg protein as a ventral signal for the induction of vg expression. Furthermore, the expression of both Ser and Wg is sufficient to trigger ectopic wing development in the wing disc and leg discs. The product of the Notch gene, which encodes a receptor, is also required for this event and we suggest that its role is to integrate the inputs of Ser and Wg. CONCLUSIONS: We show that the induction of vg, which initiates wing development in Drosophila, requires the combined activities of Ser, wg and Notch. Based on the patterns of expression and requirements for Ser and wg in this process, we propose that Ser is a dorsal signal and that Wg is a ventral signal, and that their combination at the dorso-ventral interface activates the Notch receptor and leads to vg expression.

Animals↗
PubMed1995

wingless is required for the formation of a subset of muscle founder cells during Drosophila embryogenesis.

The final pattern of the Drosophila larval body wall muscles depends critically on the prior segregation of muscle founder cells. We would like to understand the underlying molecular mechanisms which ensure the precise allocation and placement of these muscle founder cells. We have begun our analysis by examining the role of the segment polarity genes, known to be involved in the patterning of the ectoderm. Mutations in only one member of this class, wingless (wg), lead to the complete loss of a subset of muscle founder cells characterised by the expression of S59. Using the GAL4-targetted expression system, we find that Wingless, a secreted glycoprotein and well characterized signalling molecule, acts directly on the mesoderm to ensure the formation of S59-expressing founder cells. Moreover, we present evidence that Wg can signal across germ layers and that, in the wild-type embryo, Wg from the ectoderm could constitute an inductive signal for the initiation of the development of a subset of somatic muscles.

Animals↗
PubMed1994

Notch is required for wingless signaling in the epidermis of Drosophila.

Mutations in the Notch (N) gene affect many processes during the development of Drosophila. Some alleles of Notch affect only particular processes, suggesting that the Notch protein (N) has more than one functional domain. We have found a series of N mutant phenotypes that are similar to those produced by the loss of function of the segment polarity gene wingless (wg) in the embryo and the adult. In addition, we observe that mutations in N behave as dominant enhancers of wg and that there exist allele-specific interactions between the two loci. Our results suggest that the product of wg is a ligand for N.

Animals↗
PubMed1994

The wingless signalling pathway and the patterning of the wing margin in Drosophila.

The margin of the wing of Drosophila is defined and patterned from a stripe of cells expressing the wingless (wg) gene that is established during the third larval instar in the developing wing blade. The expression of the genes cut and achaete in a small domain in the prospective wing margin region reflects the activity of wg and probably mediate its function. Our results indicate that, in the wing margin, the wingless signal requires the activity of at least three genes: armadillo (arm), dishevelled (dsh) and shaggy (sgg) and that the functional relationship between these genes and wg is the same as that which exist during the patterning of the larval epidermis. These observations indicate that arm, dsh and sgg encode elements of a unique 'wingless signalling pathway' that is used several times throughout development.

Animals↗
PubMed1993

puckered, a gene involved in position-specific cell differentiation in the dorsal epidermis of the Drosophila larva.

The final pattern of the cuticle of the Drosophila larva depends on the position-specific behaviour of the epidermal cells during their differentiation. This behaviour is dictated, in part, by the relative position of the cells during embryogenesis which allows them to receive and integrate signals from their neighbours. The translation of this 'positional information' into pattern might depend on the activity of genes that are able to integrate the outcome of cell interactions and transfer it to the genes responsible for cell differentiation. Mutations in the gene puckered cause spatially restricted defects during the differentiation of the larval epidermal cells. We present data that suggests puckered may be involved in linking positional information to cell differentiation.

Animals↗
PubMed1991

Secretion and movement of wingless protein in the epidermis of the Drosophila embryo.

The segment polarity gene wingless encodes a cysteine rich protein which is essential for pattern formation in Drosophila. Using polyclonal antibodies against the product of the wingless gene, we demonstrate that this protein is secreted in the embryo and that it is taken up by neighbouring cells. The protein can be found two or three cell diameters away from the cells in which it is synthesized. We discuss the possible mechanisms which are responsible for this spatial distribution and its regulation during embryogenesis.

Alleles↗
PubMed1991

Roles of wingless in patterning the larval epidermis of Drosophila.

The larval epidermis of Drosophila shows a stereotyped segmentally repeating pattern of cuticular structures. Mutants deficient for the wingless gene product show highly disrupted patterning of the larval cuticle. We have manipulated expression of the wg gene product to assess its role in this patterning process. We present evidence for four distinct phases of wg function in epidermal cells: (1) an early requirement in engrailed-expressing cells to establish and maintain stable expression of en, (2) a discrete period when wg and en gene products act in concert to generate positional values in the anterior portion of the ventral segment and all values of the dorsal and lateral epidermis, (3) a progressive function (dependent on prior interaction with the en-expressing cells) in conferring positional values to cells within the posterior portion of the segment, and (4) a late continuous requirement for maintaining some ventral positional values.

Animals↗
PubMed1989

A cellular basis for pattern formation in the insect epidermis.

Developmental and genetic studies of the detailed patterns visible on the cuticle of many insects indicates that they are generated, progressively, through cellular interactions between nearest neighbours rather than instructed by gradients of diffusible morphogens.

Animals↗
PubMed1988

Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo.

Segment polarity genes are expressed and required in restricted domains within each metameric unit of the Drosophila embryo. We have used the expression of two segment polarity genes engrailed (en) and wingless (wg) to monitor the effects of segment polarity mutants on the basic metameric pattern. Absence of patched (ptc) or naked (nkd) functions triggers a novel sequence of en and wg patterns. In addition, although wg and en are not expressed on the same cells absence of either one has effects on the expression of the other. These observations, together with an analysis of mutant phenotypes during development, lead us to suggest that positional information is encoded in cell states defined and maintained by the activity of segment polarity gene products.

Animals↗