Search PubMed⌕ Search

Biomedical subjects

K V Anderson

Publications and source records attributed to K V Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1994

The spätzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo.

spätzle is a maternal effect gene required in the signal transduction pathway that establishes the dorsal-ventral pattern of the Drosophila embryo. spätzle acts immediately upstream of the membrane protein Toll in the genetic pathway, suggesting that spätzle could encode the ventrally localized ligand that activates the receptor activity of Toll. The spätzle gene encodes a novel secreted protein that appears to require activation by a proteolytic processing reaction, which is controlled by the genes that act upstream of spätzle in the genetic pathway. We propose that proteolytic processing of the spätzle protein is confined to the ventral side of the embryo and that the localization of processed spätzle determines where the receptor, Toll, is active.

Amino Acid Sequence↗
PubMed1994

A processed form of the Spätzle protein defines dorsal-ventral polarity in the Drosophila embryo.

Stein et al. (1991) identified a soluble, extracellular factor that induces ventral structures at the site where it is injected in the extracellular space of the early Drosophila embryo. This factor, called polarizing activity, has the properties predicted for a ligand for the transmembrane receptor encoded by the Toll gene. Using a bioassay to follow activity, we purified a 24 x 10(3) M(r) protein that has polarizing activity. The purified protein is recognized by antibodies to the C-terminal half of the Spätzle protein, indicating that this polarizing activity is a product of the spätzle gene. The purified protein is smaller than the primary translation product of spätzle, suggesting that proteolytic processing of Spätzle on the ventral side of the embryo is required to generate the localized, active form of the protein.

Animals↗
PubMed1993

Genetic characterization of tube and pelle, genes required for signaling between Toll and dorsal in the specification of the dorsal-ventral pattern of the Drosophila embryo.

tube and pelle are two of the maternally transcribed genes required for dorsal-ventral patterning of the Drosophila embryo. Females homozygous for strong alleles of tube or pelle produce embryos that lack all ventral and lateral embryonic pattern elements. By analyzing the phenotypes caused by 24 pelle and 9 tube alleles, we have defined characteristic features of the two genes, including the extremely variable phenotypes of a number of tube alleles and the antimorphic character of a number of pelle alleles. Double mutant females carrying dominant ventralizing alleles of Toll and dorsalizing alleles of tube or pelle produce dorsalized embryos, suggesting that tube and pelle act downstream of the membrane protein Toll in the signaling pathway that defines the embryonic dorsal-ventral pattern. Both tube and pelle are also important zygotically for survival: at least 30% of the zygotes lacking either tube or pelle die before adult stages, while 90-95% of tube- pelle- double mutant zygotes die. We discuss the phenotypes of tube-pelle double mutants in the context of whether the two proteins interact directly.

Alleles↗
PubMed1992

Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo.

Zygotic expression of the Drosophila TGF beta family member decapentaplegic (dpp) is required for the development of the dorsal embryonic structures. By injecting dpp transcripts into young embryos, we find that 2- to 4-fold increases in the concentration of injected RNA elicit progressively more dorsal cell fates: only low levels of dpp permit development of ventral ectoderm, intermediate dpp levels drive dorsal epidermal development, and high dpp levels drive cells to differentiate as the most dorsal pattern element, the amnioserosa. Localized dpp RNA injections into embryos that lack all known maternal and zygotic dorsal-ventral polarity indicate that dpp can both define embryonic polarity and organize detailed patterning within the ectoderm. We infer that dpp acts as an extracellular morphogen and that the graded activity of dpp specifies the pattern of ectodermal cell fates in the Drosophila embryo.

Animals↗
PubMed1992

Extracellular proteases and embryonic pattern formation.

At least three genes that play crucial roles in dorsal-ventral patterning of the Drosophila embryo appear to encode extracellular proteases. These proteases are involved in the generation of localized extracellular ligands for membrane receptors. Because the sequences of these gene products closely resemble those of mammalian enzymes that have been studied in detail biochemically, it is possible to draw on the wealth of information on the biochemical mechanisms that regulate protease activity to make inferences about how proteases can be used to generate spatial asymmetries within fields of cells.

Journal Article↗
PubMed1992

Localized enhancement and repression of the activity of the TGF-beta family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo.

Seven zygotically active genes are required for normal patterning of the dorsal 40% of the Drosophila embryo. Among these genes, decapentaplegic (dpp) has the strongest mutant phenotype: in the absence of dpp, all cells in the dorsal and dorsolateral regions of the embryo adopt fates characteristic of more ventrally derived cells (Irish and Gelbart (1987) Genes Dev. 1, 868-879). Here we describe the phenotypes caused by alleles of another of this set of genes, tolloid, and show that tolloid is required for dorsal, but not dorsolateral, pattern. Extragenic suppressors of tolloid mutations were isolated that proved to be mutations that elevate dpp activity. We studied the relationship between tolloid and dpp by analyzing the phenotypes of tolloid embryos with elevated numbers of the dpp gene and found that doubling the dpp+ gene dosage completely suppressed weak tolloid mutants and partially suppressed the phenotypes of tolloid null mutants. We conclude that the function of tolloid is to increase dpp activity. We also examined the effect of doubling dpp+ gene dosage on the phenotypes caused by other mutations affecting dorsal development. Like tolloid, the phenotypes of mutant embryos lacking shrew gene function were suppressed by elevated dpp, indicating that shrew also acts upstream of dpp to increase dpp activity. In contrast, increasing the number of copies of the dpp gene enhanced the short gastrulation (sog) mutant phenotype, causing ventrolateral cells to adopt dorsal fates. This indicates that sog gene product normally blocks dpp activity ventrally. We propose that the tolloid, shrew and sog genes are required to generate a gradient of dpp activity, which directly specifies the pattern of the dorsal 40% of the embryo.

Animals↗
PubMed1992

Activation of the easter zymogen is regulated by five other genes to define dorsal-ventral polarity in the Drosophila embryo.

The product of the Drosophila easter gene, a member of the trypsin family of serine proteases, must be more active ventrally than dorsally to promote normal embryonic polarity. The majority of the easter protein in the embryo is present in the unprocessed zymogen form and appears to be evenly distributed in the extracellular space, indicating that the asymmetric activity of wild-type easter must arise post-translationally. A dominant mutant form of easter that does not require cleavage of the zymogen for activity (ea delta N) is active both dorsally and ventrally. The ea delta N mutant bypasses the requirement for five other maternal effect genes, indicating that these five genes exert their effects on dorsal-ventral patterning solely by controlling the activation of the easter zymogen. We propose that dorsal-ventral asymmetry is initiated by a ventrally-localized molecule in the vitelline membrane that nucleates an easter zymogen activation complex, leading to the production of ventrally active easter enzyme.

Animals↗
PubMed1991

Dominant and recessive mutations define functional domains of Toll, a transmembrane protein required for dorsal-ventral polarity in the Drosophila embryo.

The asymmetry of the dorsal-ventral pattern of the Drosophila embryo appears to depend on the ventral activation of the transmembrane Toll protein. The Toll protein is found around the entire dorsal-ventral circumference of the embryo, and it appears to act as a receptor for a ventral, extracellular signal and to then relay that signal to the cytoplasm in ventral regions of the embryo. Three of five recessive loss-of-function alleles of Toll are caused by point mutations in the region of the cytoplasmic domain of Toll that is similar to the mammalian interleukin-1 receptor, supporting the hypothesis that Toll acts as a signal-transducing receptor. Nine dominant gain-of-function alleles that cause Toll to be active in dorsal, as well as ventral, regions of the embryo are caused by mutations in the extracellular domain. Three of the dominant alleles appear to cause the protein to be constitutively active and are caused by cysteine-to-tyrosine changes immediately outside the transmembrane domain. All six of the remaining dominant alleles require the presence of a wild-type transmembrane Toll protein for their ventralizing effect and all encode truncated proteins that lack the transmembrane and cytoplasmic domains.

Alleles↗
PubMed1991

Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: importance of transmembrane signaling for dorsal-ventral pattern formation.

Formation of the Drosophila embryo's dorsal-ventral pattern requires the maternal product of the Toll gene. DNA sequence and genetic analyses together suggested that the Toll gene product is a transmembrane protein which communicates information from an extracytoplasmic compartment to the cytoplasm. Using antibodies as probes, we show that the Toll protein is a 135 x 10(3) Mr glycoprotein which is tightly associated with embryonic membranes. During the syncytial stage when dorsal-ventral polarity is established, the maternal Toll protein is associated with the plasma membrane around the entire embryo. During later embryonic stages, the Toll protein is expressed zygotically on many cell surfaces, possibly to promote cell adhesion. The plasma membrane localization of the Toll protein in the syncytial embryo suggests that transmembrane signaling from the extracellular perivitelline space to the cytoplasm is required for establishment of the embryonic dorsal-ventral pattern.

Animals↗
PubMed1990

Dominant and recessive alleles of the Drosophila easter gene are point mutations at conserved sites in the serine protease catalytic domain.

The easter gene, required for the development of all lateral and ventral pattern elements in the Drosophila embryo, appears to encode an extracellular serine protease. Dominant easter alleles increase the number of cells that give rise to lateral and ventral structures. We have found that nine dominant and four recessive mutations are caused by single amino acid substitutions at conserved sites in the putative serine protease catalytic domain. The activity of dominant products was assayed by injecting in vitro synthesized transcripts from the dominant alleles into young embryos. The results suggest that the dominant easter products cleave the normal substrate, but fail to respond to a spatially asymmetric regulator.

Alleles↗
PubMed1989

The role of easter, an apparent serine protease, in organizing the dorsal-ventral pattern of the Drosophila embryo.

The maternally transcribed product of the Drosophila easter gene is essential for the establishment of a normal dorsal-ventral pattern in embryos. Loss-of-function mutations in easter result in a dorsalization of the embryonic pattern, while dominant gain-of-function mutations ventralize the embryonic pattern. P element insertion alleles of easter were isolated and used to identify genomic and cDNA clones that include the easter gene. Injection of in vitro-synthesized transcripts of the cDNA into embryos from easter mutant females completely rescued the mutant phenotype, allowing normal development. This result confirmed that the cDNA encodes easter and that the easter product is only required after fertilization. The sequence of the cDNA suggests that the product of the easter gene is an extracytoplasmic serine protease. The implications of the dominant alleles of this putative protease for the mechanism of dorsal-ventral pattern formation are discussed.

Alleles↗
PubMed1988

The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein.

The Toll gene of Drosophila, a maternal effect gene that plays a central role in the establishment of the embryonic dorsal-ventral pattern, has been cloned using P element tagging. A 5.3 kb poly(A)+ ovarian transcript from the cloned region was purified by hybrid selection with the cloned DNA. This purified transcript complements the Toll mutant phenotype when injected into Toll- embryos, which proves that it is the Toll transcript. The sequence of cDNAs suggests that the Toll protein is an integral membrane protein with a cytoplasmic domain and a large extracytoplasmic domain. The putative extracytoplasmic domain contains at least 15 repeats of a 24 amino acid, leucine-rich sequence found in both human and yeast membrane proteins.

Alleles↗
PubMed1988

Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation.

Maternal expression of the Toll gene is required for the production and the correct spatial organization of all lateral and ventral structures of the Drosophila embryo. We show here that the Toll gene is transcribed zygotically in the embryo and that zygotic expression is important for the viability of the larva. Both genetic and molecular data indicate that the zygotic Toll product has the same biochemical activity as the maternal product. The spatial distribution of the Toll transcript in the embryo was analyzed. In contrast to the uniform distribution of the maternal RNA, the zygotic Toll RNA is present in a complex spatial and temporal pattern in the embryo. A striking feature of this pattern is the correlation of the regions of invaginating cells with sites of accumulation of zygotic Toll RNA.

Animals↗
PubMed1985

Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product.

Within the group of maternal effect genes necessary for the establishment of the dorsal-ventral pattern of the Drosophila embryo, the Toll gene mutates to give a singular variety of embryonic phenotypes. Lack of function alleles produce dorsalized embryos as a recessive maternal effect. Dominant gain of function alleles result in ventralized embryos. Other recessive alleles cause partial dorsalization or lateralization of the embryonic pattern. Gene dosage studies indicate that the dominant ventralized phenotype results from an altered activity of the Toll product. Complementation studies show specific trans interactions between copies of the Toll product. Double mutant phenotypes suggest that the products of several other dorsal-group genes regulate the activity of Toll.

Alleles↗
PubMed1985

Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product.

Drosophila females that lack Toll gene activity produce dorsalized embryos, in which all embryonic cells behave like the dorsal cells of the wild-type embryo. Injection of wild-type cytoplasm into young Toll- embryos restores their ability to produce a normal dorsal-ventral pattern in a position-dependent manner. No matter where the cytoplasm is injected relative to the dorsal-ventral axis of the egg shell, the position of the injected cytoplasm defines the ventralmost part of the rescued pattern. Although injection of wild-type cytoplasm into mutants at six other dorsal-group loci also restores the ability to produce lateral and ventral structures, only Toll- embryos lack any residual dorsal-ventral polarity. Experiments suggest that the activity of the Toll product is normally regulated by other dorsal-group genes and that the function of the Toll product is to provide the source for a morphogen gradient in the dorsal-ventral axis of the wild-type embryo.

Animals↗
PubMed1985

Localization and morphometric analysis of masticatory muscle afferent neurons in the nucleus of the mesencephalic root of the trigeminal nerve in the cat.

Injections of horseradish peroxidase (HRP) were made into the ipsilateral temporal muscle and contralateral masseter muscle of 10 cats in order to identify and characterize neurons in the nucleus of the mesencephalic root of the trigeminal nerve that innervate muscle receptors in the orofacial periphery. Neurons labelled by HRP injections and unlabelled cells from 5 control cats were measured with a computer-based image analyzer, and their position was mapped on a stereotaxic graph. Cells that innervate the masseter and temporal muscles were identified throughout the rostrocaudal extent of the nucleus. There was no indication of a somatotopic pattern nor of a specific segregation within the nucleus for cells innervating muscle receptors. The nucleus contained small, rounded unipolar neurons located primarily in the dorsal border of the periaqueductal gray (PAG) matter in the rostral part of the nucleus and larger oval unipolar neurons which were scattered throughout the nucleus, but were predominant in the pontine portion of the nucleus. HRP injections labelled both large and small cells, as well as occasional multipolar cells. The last-mentioned tended to be located in the lateral margins of the PAG. The mean geometric values obtained for the control group were: area 552.7 microns2 perimeter 110.3 microns; maximum diameter 36.0 microns. and diameter of an equivalent circle 26.1 microns. The mean values of the labelled neurons were: area 606.6 microns2; perimeter 100.1 microns; maximum diameter 36.0 microns, and diameter of an equivalent circle 27.2 microns.

Animals↗