Biomedical subjects

K Basler

Publications and source records attributed to K Basler.

At least 37 records · Page 2Linked to original sources

PubMed1997

pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.

Members of the Wnt/Wingless (Wg) family of signalling proteins organize many aspects of animal development by regulating the expression of particular target genes in responding cells. Recent biochemical studies indicate that the vertebrate HMG-domain proteins Lef-1 and XTcf-3 can physically interact with beta-catenin, a homologue of Drosophila Armadillo (Arm), the most downstream component known in the Wnt signal transduction pathway. However, these studies do not address whether the endogenous Lef/Tcf family members are required in vivo to transduce Wnt signals. Using genetic methods in Drosophila, we define a new segment polarity gene, pangolin (pan), and show that its product is required in vivo for Wg signal transduction in embryos and in developing adult tissues. In addition, we show that pan encodes a Lef/Tcf homologue and provide evidence that its protein product binds to the beta-catenin homologue Armadillo in vivo. Finally, we demonstrate that Pan functions downstream of Arm to transduce the Wg signal. Thus, our results indicate that Pan is an essential component of the Wg transduction pathway and suggest that it acts directly to regulate gene transcription in response to Wg signalling.

Amino Acid Sequence↗

PubMed1997

Hedgehog signaling in Drosophila eye and limb development - conserved machinery, divergent roles?

The secreted signaling molecule Hedgehog plays a key role in patterning Drosophila eyes and limbs. Recently, the transmembrane proteins Patched and Smoothened and the Gli protein Cubitus interruptus have been identified as essential components in Hedgehog signal transduction. Progress has also been made in understanding the function of Decapentaplegic (Dpp) in mediating the Hedgehog signal. Although playing only a minor role in the eye, Dpp governs, at long range, the expression of essential genes such as optomotor blind and spalt in the wing.

Animals↗

PubMed1996

Direct and long-range action of a wingless morphogen gradient.

Wingless (Wg), a founding member of the Wingless/Int-1 (Wnt) family of secreted proteins, acts as a short-range inducer and as a long-range organizer during Drosophila development. Here, we determine the consequences of ectopically expressing (i) a wild-type form of Wg, (ii) a membrane-tethered form of Wg, and (iii) a constitutively active form of the cytosolic protein Armadillo (Arm), which normally acts to transduce Wg, and we compare them with the effects of removing endogenous Wg or Arm activity. Our results indicate that wild-type Wg acts at long range, up-regulating the transcription of particular target genes as a function of concentration and distance from secreting cells. In contrast, tethered Wg and Arm have only short-range or autonomous effects, respectively, on the transcription of these genes. We interpret these findings as evidence that Wg can act directly and at long range as a gradient morphogen during normal development.

Animals↗

PubMed1996

Hedgehog-dependent patterning in the Drosophila eye can occur in the absence of Dpp signaling.

The progression of retinal morphogenesis in the Drosophila eye is controlled to a large extent by Hedgehog (Hh), a signaling protein emanating from differentiating photoreceptor cells. Adjacent, more anterior cells in the morphogenetic furrow respond to Hh by expressing decapentaplegic (dpp), suggesting that the relationship between Hh and Dpp might be similar to that in the limb imaginal discs where Dpp mediates the organizing activity of Hh. In this study we show that this is not the case. Analysis of somatic clones of cells lacking the Dpp receptors Punt or Tkv reveals that Dpp plays only a minor role in furrow progression and no critical role in subsequent ommatidial development. In contrast, Hh-independent dpp expression around the posterior and lateral margins of the first and second instar eye discs is important for the growth of the eye disc and for initiation of the morphogenetic furrow at these margins.

Animals↗

PubMed1996

Sending and receiving the hedgehog signal: control by the Drosophila Gli protein Cubitus interruptus.

Drosophila limb development is organized by interactions between anterior and posterior compartment cells. Posterior cells continuously express and require engrailed (en) and secrete Hedgehog (Hh) protein. Anterior cells express the zinc-finger protein Cubitus interruptus (Ci). It is now shown that anterior cells lacking ci express hh and adopt posterior properties without expressing en. Increased levels of Ci can induce the expression of the Hh target gene decapentaplegic (dpp) in a Hh-independent manner. Thus, expression of Ci in anterior cells controls limb development (i) by restricting hh secretion to posterior cells and (ii) by conferring competence to respond to Hh by mediating the transduction of this signal.

Animals↗

PubMed1996

Direct and long-range action of a DPP morphogen gradient.

During development of the Drosophila wing, the decapentaplegic (dpp) gene is expressed in a stripe of cells along the anteroposterior compartment boundary and gives rise to a secreted protein that exerts a long-range organizing influence on both compartments. Using clones of cells that express DPP, or in which DPP receptor activity has been constitutively activated or abolished, we show that DPP acts directly and at long range on responding cells, rather than by proxy through the short-range induction of other signaling molecules. Further, we show that two genes, optomotor-blind and spalt are transcriptionally activated at different distances from DPP-secreting cells and provide evidence that these genes respond to different threshold concentrations of DPP protein. We propose that DPP acts as a gradient morphogen during wing development.

Animals↗

PubMed1996

Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing.

The mammalian growth factor TGFbeta negatively regulates cell proliferation in various systems. Here we provide evidence that another TGFbeta superfamily member, Drosophila Decapentaplegic (Dpp), stimulates cell proliferation. In the developing wing blade, somatic clones lacking the Dpp receptors Punt or Thick veins (Tkv), or lacking Schnurri, a transcription factor involved in Dpp signal interpretation, fail to grow when induced early in larval development. Furthermore the spatial requirement for these signaling components indicates that Dpp has to travel several cell diameters from its source in order to reach all cells that require its signal. The requirement for Tkv also depends on the distance of cells from the source of the Dpp signal. We propose that Dpp can act at a distance to positively control cell proliferation.

Animals↗

PubMed1995

Schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1.

Cytokines of the TGF beta superfamily regulate many aspects of cellular function by activating receptor complexes consisting of two distantly related serine/threonine kinases. Previous studies have indicated that Drosophila dpp uses similar signaling complexes and strictly requires the punt and thick veins receptors to transduce the signal across the membrane. Here, we show that the schnurri (shn) gene is required for many aspects of dpp signaling. Genetic epistasis experiments indicate that shn functions downstream of the dpp signal and its receptors. The shn gene encodes a large protein similar to a family of mammalian zinc finger transcription factors. The shn protein might therefore act as a nuclear target in the dpp signaling pathway directly regulating the expression of dpp-responsive genes.

Activin Receptors↗

PubMed1995

An absolute requirement for both the type II and type I receptors, punt and thick veins, for dpp signaling in vivo.

TGF beta elicits diverse cellular responses by signaling through receptor complexes formed by two distantly related transmembrane serine/threonine kinases called type II and type I receptors. Previous studies have indicated that the product of the Drosophila thick veins (tkv) gene is a type I receptor for decapentaplegic (dpp). Here, we show that the Drosophila gene punt encodes a homolog of a vertebrate type II receptor, and we demonstrate that punt, like tkv, is essential in vivo for dpp-dependent patterning processes. Because no dpp-related signalling is apparent in the absence of either the punt or tkv receptor, we infer that both receptors act in concert to transduce the dpp signal and that their functions cannot be replaced by the other extant type II and I receptors.

Activin Receptors↗

PubMed1995

Sequential organizing activities of engrailed, hedgehog and decapentaplegic in the Drosophila wing.

The Drosophila wing is formed by two cell populations, the anterior and posterior compartments, which are distinguished by the activity of the selector gene engrailed (en) in posterior cells. Here, we show that en governs growth and patterning in both compartments by controlling the expression of the secreted proteins hedgehog (hh) and decapentaplegic (dpp) as well as the response of cells to these signaling molecules. First, we demonstrate that en activity programs wing cells to express hh whereas the absence of en activity programs them to respond to hh by expressing dpp. As a consequence, posterior cells secrete hh and induce a stripe of neighboring anterior cells across the compartment boundary to secrete dpp. Second, we demonstrate that dpp can exert a long-range organizing influence on surrounding wing tissue, specifying anterior or posterior pattern depending on the compartmental provenance, and hence the state of en activity, of the responding cells. Thus, dpp secreted by anterior cells along the compartment boundary has the capacity to organize the development of both compartments. Finally, we report evidence suggesting that dpp may exert its organizing influence by acting as a gradient morphogen in contrast to hh which appears to act principally as a short range inducer of dpp.

Animals↗

PubMed1994

Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic.

Members of the TGF beta superfamily of secreted signaling molecules regulate growth and cellular patterning during development and interact with specific type I and type II membrane receptors possessing a cytoplasmic serine/threonine kinase domain. We describe two members of the type I receptor family in Drosophila and demonstrate that they are encoded by the genes saxophone (sax) and thick veins (tkv). Further, we show that mutations that abolish sax or tkv activity cause phenotypes similar to partial or complete loss of activity, respectively, of the TGF beta homolog decapentaplegic (dpp). We propose that specification of distinct cell fates in response to different concentrations of dpp may be achieved combinatorially by the sax and tkv receptors.

Amino Acid Sequence↗

PubMed1994

Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.

Drosophila limbs are subdivided into anterior and posterior compartments which derive from adjacent cell populations founded early in development. Evidence is now provided that posterior cells organize growth and cell patterning in both compartments by secreting hedgehog protein and that hedgehog protein acts indirectly by inducing neighbouring anterior cells to secrete decapentaplegic or wingless protein.

Animals↗

PubMed1994

Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis.

Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.

Animals↗

PubMed1993

Control of cell pattern in the neural tube: regulation of cell differentiation by dorsalin-1, a novel TGF beta family member.

Distinct cell types differentiate along the dorsoventral axis of the neural tube. We have cloned and characterized a novel member of the TGF beta gene family, dorsalin-1 (dsl-1), that appears to regulate cell differentiation within the neural tube. dsl-1 is expressed selectively in the dorsal neural tube, and its pattern of expression appears to be restricted by early signals from the notochord. Exposure of neural plate cells to dsl-1 promotes the differentiation of cells with neural crest-like properties and inhibits the induction of motor neurons by signals from the notochord and floor plate. These findings suggest that dsl-1 regulates the differentiation of cell types along the dorsoventral axis of the neural tube, acting in conjunction with distinct ventralizing signals from the notochord and floor plate.

Amino Acid Sequence↗

PubMed1993

Organizing activity of wingless protein in Drosophila.

The adult appendages of Drosophila are formed from imaginal discs, sheets of epithelial cells that proliferate during larval development and differentiate during metamorphosis. wingless (wg, DWnt-1) protein, a putative signaling molecule, is expressed only in prospective ventral cells in each of the leg discs. To test the role of wg, we have generated randomly positioned clones of cells that express wg protein constitutively. Clones that arise in the prospective ventral portions of the leg discs develop normally. In contrast, dorsally situated clones give rise to ventrolateral patterns and exert a ventralizing influence on neighboring wild-type tissue. We propose that wg protein organizes leg pattern along the dorsoventral axis by conferring ventral positional information within the disc.

Animals↗

PubMed1993

Ras1-dependent signaling by ectopically-expressed Drosophila src gene product in the embryo and developing eye.

The cellular functions of the Drosophila src 64B (Dsrc) gene product, Dsrc, and of most vertebrate Src-family kinases, are unknown. We have examined the effects of over-expression of wild type and mutated forms of Dsrc in transgenic Drosophila. Expression of both wild type Dsrc and a C-terminally truncated mutant at high levels during embryonic development induced extensive tyrosine phosphorylation of cellular proteins and caused considerable lethality, correlating with a block to germ-band retraction. Over-expression in the eye imaginal disc led to excess production of photoreceptor cells in the adult ommatidia. In contrast, expression of a kinase-inactive form of Dsrc caused distinct nervous system abnormalities in embryos and decreased the numbers of photoreceptor cells in the adult eye ommatidia. This suggests that active forms of Dsrc alter development by phosphorylation. Both the lethality and the eye roughening caused by activated Dsrc were partially suppressed by mutations in the Drosophila Ras1 gene. These results suggest that over-expressed Dsrc may function through Ras1 to stimulate differentiation in the embryonic nervous system and eye imaginal disc, and that kinase-active Dsrc interferes with these processes.

Animals↗

PubMed1992

The paired box gene pox neuro: a determinant of poly-innervated sense organs in Drosophila.

This study describes the structure and function of pox neuro (poxn), a gene previously isolated by virtue of a conserved domain, the paired box, which it shares with the segmentation genes paired and gooseberry. Its expression pattern has been analyzed, particularly during development of the PNS. We propose that poxn is a "neuroblast identity" gene acting in both the PNS and the CNS on the basis of the following evidence. Its expression is restricted to four neuronal precursors in each hemisegment: two neuronal stem cells (neuroblasts) in the CNS, and two sensory mother cells (SMCs) in the PNS. The SMCs that express poxn produce the poly-innervated external sense organs of the larva. In poxn- embryos, poly-innervated sense organs are transformed into mono-innervated. Conversely, ectopic expression of poxn in embryos transformed with a heat-inducible poxn gene can switch mono-innervated to poly-innervated sense organs. Expression of poxn in the wing disc is restricted to the SMCs of the poly-innervated sense organs, suggesting that poxn also determines the lineage of poly-innervated adult sense organs.

Amino Acid Sequence↗

PubMed1991

Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye.

Cell fate in the developing eye is determined by a cascade of inductive interactions. In this process, the sevenless protein--a receptor tyrosine kinase--is required for the specification of the R7 photoreceptor cell fate. We have constructed a gain-of-function sevenless mutation (SevS11) by overexpressing a truncated sevenless protein in the cells where sevenless is normally expressed. In SevS11 mutant flies, all sevenless-expressing cells initiate neural development. This results in the formation of multiple R7-like photoreceptors per ommatidium. Therefore, sevenless activity appears to be necessary and sufficient for the determination of R7 cell fate. These results illustrate the central role receptor tyrosine kinases can play in the specification of cell fate during development.

Animals↗