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C S Goodman

Publications and source records attributed to C S Goodman.

At least 109 records · Page 6Linked to original sources

Analysis of the gooseberry locus in Drosophila embryos: gooseberry determines the cuticular pattern and activates gooseberry neuro.

The segment-polarity class of segmentation genes in Drosophila are primarily involved in the specification of sub-segmental units. In addition, some of the segment-polarity genes have been shown to specify cell fates within the central nervous system. One of these loci, gooseberry, consists of two divergently transcribed genes, gooseberry and gooseberry neuro, which share a paired box as well as a paired-type homebox. Here, the expression patterns of the two gooseberry gene products are described in detail. The gooseberry protein appears in a characteristic segment-polarity pattern of stripes at gastrulation and persists until head involution. It is initially restricted to the ectodermal and neuroectodermal germ layer, but is later detected in mesodermal and neuronal cells as well. The gooseberry neuro protein first appears during germ band extension in cells of the central nervous system and also, much later, in epidermal stripes and in a small number of muscle cells. P-element-mediated transformation with the gooseberry gene has been used to demonstrate that gooseberry transactivates gooseberry neuro and is sufficient to rescue the gooseberry cuticular phenotype in the absence of gooseberry neuro.

Animals↗

Genetic analysis of laminin A reveals diverse functions during morphogenesis in Drosophila.

In order to dissect the functions of laminin A in vivo, we have undertaken a molecular and genetic characterization of the laminin A subunit (lamA) gene in Drosophila. Sequence analysis predicts a multidomain structure similar to mammalian homologs. We generated a series of complete and partial loss-of-function mutant alleles of the lamA gene; complete loss-of-function mutations lead to late embryonic lethality. Certain combinations of partial loss-of-function lamA alleles give rise to escaper adults, which have rough eyes associated with changes in cell fate and pattern, misshapen legs and defects in wing structure. These phenotypes suggest that laminin A has diverse functions during morphogenesis in Drosophila.

Animals↗

Ectopic expression of seven-up causes cell fate changes during ommatidial assembly.

During Drosophila ommatidial development, a single cell is selected within the ommatidial cluster to become the R7 photoreceptor neuron. The seven-up gene has been shown to play a role in this process by preventing four other photoreceptor precursors, R3/R4/R1/R6, from adopting the R7 cell fate. The seven-up gene encodes a steroid receptor-like molecule that is expressed only in those four cells that require seven-up function in the developing Drosophila ommatidium. We have examined the functional significance of the spatially restricted expression of seven-up by misexpressing seven-up isoforms. As expected from the function that seven-up performs in R3/R4/R1/R6, ubiquitous expression of seven-up causes transformation of the R7 cell to an R1-R6 cell fate. In addition, depending on the timing and spatial pattern of expression, various other phenotypes are produced including the loss of the R7 cell and the formation of extra R7 cells. Ubiquitous expression of seven-up close to the morphogenetic furrow interferes with R8 differentiation resulting in failure to express the boss protein, the ligand for the sevenless receptor tyrosine kinase, and the R7 cell is lost consequently. Extra R7 cells are formed by recruiting non-neuronal cone cells as photoreceptor neurons in a sevenless and bride of sevenless independent way. Thus, the spatiotemporal pattern of seven-up expression plays an essential role in controlling the number and cellular origin of the R7 neuron in the ommatidium. Our results also suggest that seven-up controls decisions not only between photoreceptor subtypes, but also between neuronal and non-neuronal fates.

Animals↗

From growth cone to synapse: the life history of the RP3 motor neuron.

In Drosophila, the ability to analyze the development of individually identified neurons with a variety of imaging and biophysical techniques can be complemented by sophisticated genetics and molecular biology. This powerful combination is allowing the development and function of single neurons and their synaptic connections to be unraveled at an unparalleled level of resolution. In this article, we focus on a single, identified motoneuron--RP3--arguably the best understood neuron in the fruitfly. Many events in the life history of RP3 are well characterized, including cell migration, axon outgrowth and pathfinding within the central nervous system, pathfinding in the periphery to its appropriate muscle target domain, the specific recognition of its muscle targets, the events of synapse formation and maturation, and its mature function in the locomotion of the fly larva. Genetic analysis has revealed mutations in a number of different genes which affect specific aspects of RP3 development from axon outgrowth to synapse formation.

Animals↗

To cross or not to cross: a genetic analysis of guidance at the midline.

Previous studies have led to the suggestion that the midline of the developing Drosophila central nervous system might serve a dual function during growth cone guidance, providing attractive signals for those growth cones that project across the midline, and at the same time repulsive signals for those growth cones that stay on only their own side. In an attempt to discover some of the genes encoding key components of these two guidance systems, we performed a large-scale screen in Drosophila for mutants that affect the development of the axon commissures. Here we review the mutant phenotypes of two new genes in which either too few (commissureless) or too many (roundabout) growth cones cross the midline. These phenotypes suggest that these two genes encode important components for growth cone guidance at the midline.

Alleles↗

Connectin: a homophilic cell adhesion molecule expressed on a subset of muscles and the motoneurons that innervate them in Drosophila.

Each abdominal hemisegment in the Drosophila embryo contains a stereotyped array of 30 muscles, each specifically innervated by one or a few motoneurons. We screened 11,000 enhancer trap lines, isolated several expressing beta-galactosidase in small subsets of muscle fibers prior to innervation, and identified two of these as inserts in connectin and Toll, members of the leucine-rich repeat gene family. Connectin contains a signal sequence, ten leucine-rich repeats, and a putative phosphatidylinositol membrane linkage; in S2 cells, connectin can mediate homophilic cell adhesion. Connectin is expressed on the surface of eight muscles, the motoneurons that innervate them, and several glial cells along the pathways leading to them. During synapse formation, the protein localizes to synaptic sites; afterward, it largely disappears. Thus, connectin is a novel cell adhesion molecule whose expression suggests a role in target recognition.

Amino Acid Sequence↗

The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye.

The argos gene encodes a protein that is required for viability and that regulates the determination of cells in the Drosophila eye. A developmental analysis of argos mutant eyes indicates that the mystery cells, which are usually nonneuronal, are transformed into extra photoreceptors, and that supernumerary cone cells and pigment cells are also recruited. Clonal analysis indicates that argos acts nonautonomously and can diffuse over the range of several cell diameters. Conceptual translation of the argos gene suggests that it encodes a secreted protein.

Amino Acid Sequence↗

Changing role of even-skipped during the evolution of insect pattern formation.

The development of Drosophila is typical of the so-called long germband mode of insect development, in which the pattern of segments is established by the end of the blastoderm stage. Short germband insects, such as the grasshopper Schistocerca americana, by contrast, generate all or most of their metameric pattern after the blastoderm stage by the sequential addition of segments during caudal elongation. This difference is discernible at the molecular level in the pattern of initiation of the segment polarity gene engrailed, and the homeotic gene abdominal-A (ref. 5). For example, in both types of insects, engrailed is expressed by the highly conserved germband stage in a pattern of regularly spaced stripes, one stripe per segment. In Drosophila, the complete pattern is visible by the end of the blastoderm stage, although engrailed appears initially in alternate segments in a pair-rule pattern that reflects its known control by pair-rule genes such as even-skipped. In contrast, in the grasshopper, the engrailed stripes appear one at a time after the blastoderm stage as the embryo elongates. To address the molecular basis for this difference, we have cloned the grasshopper homologue of the Drosophila pair-rule gene even-skipped and show that it does not serve a pair-rule function in early development, although it does have a similar function in both insects during neurogenesis later in development.

Amino Acid Sequence↗

Position-specific expression of the annulin protein during grasshopper embryogenesis.

Annulin, named for its annular expression in developing limb buds, is a approximately 100 kDa membrane-associated protein that is expressed in a complex and changing pattern during grasshopper embryogenesis. Its expression is dynamic along the developing midline and in the mesoderm, transient in neuroepithelial sheath cells around mitotic neuroblasts, and position-specific in circumferential stripes in each limb bud segment. Annulin expression begins along the midline of the embryo at the onset of gastrulation. Mesoderm cells express the protein as they migrate away from the midline as do new cells that come to lie at the midline. During neurogenesis, annulin expression disappears from many midline cells until only a specific subset of midline glial cells expresses high levels of the protein. Starting at the beginning of neurogenesis, sheath cells express annulin in correlation with the mitotic activity of the neuroblasts they surround.

Animals↗

Annulin, a protein expressed at limb segment boundaries in the grasshopper embryo, is homologous to protein cross-linking transglutaminases.

Annulin, a protein whose general stage- and position-specific expression pattern in the grasshopper embryo is described in the companion paper, is expressed in epithelial annuli in developing limbs. Here, we show that these annuli comprise narrow circumferential bands of epithelial cells at the boundaries of limb segments. At most boundaries, expression of annulin precedes the first morphological signs of segmentation. The most distal cells in a band underlie the boundary invagination. Bands arise in a stereotyped order and, within a band, expression occurs in an ordered circumferential progression. Annulin has a molecular weight of about 97 kDa and appears to be intracellular and peripherally associated with the inner leaflet of the cell membrane. Using the monoclonal antibody 7H7, two overlapping cDNA clones encoding this protein were isolated from an embryonic Schistocerca cDNA expression library. The nucleotide and deduced amino acid sequences indicate that the annulin protein does not contain either a signal sequence or a transmembrane domain. By sequence comparison, annulin appears to be a transglutaminase, one of a family of enzymes that have protein cross-linking activity. Its expression pattern within the limb and the embryo is associated with areas undergoing morphogenetic rearrangements, movements, or rapid cell division. It may stabilize cells under mechanical stress or participate in some other way in these morphogenetic activities.

Amino Acid Sequence↗

Fasciclin IV: sequence, expression, and function during growth cone guidance in the grasshopper embryo.

Monoclonal antibody 6F8 was used to characterize and clone fasciclin IV, a new axonal glycoprotein in the grasshopper, and to study its function during growth cone guidance. Fasciclin IV is dynamically expressed on a subset of axon pathways in the developing CNS and on circumferential bands of epithelial cells in developing limb buds. One of these bands corresponds to the location where the growth cones of the Ti1 pioneer neurons make a characteristic turn while extending toward the CNS. Embryos cultured in the 6F8 antibody or Fab exhibit aberrant formation of this axon pathway. cDNA sequence analysis suggests that fasciclin IV has a signal sequence; long extracellular, transmembrane, and short cytoplasmic domains; and shows no homology with any protein in the available data bases. Thus, fasciclin IV appears to be a novel integral membrane protein that functions in growth cone guidance.

Amino Acid Sequence↗

The presumptive R7 cell of the developing Drosophila eye receives positional information independent of sevenless, boss and sina.

Studies on the development of the R7 photoreceptor in the Drosophila eye thus far have identified three genes that specifically affect this cell: sevenless, boss and sina. In each of these mutants the R7 precursor develops instead as the equatorial cone cell (EQC). We have isolated an enhancer trap line, H214, in which beta-galactosidase is primarily expressed in the R7 cell throughout its development. In mutations of sevenless, boss and sina, expression in H214 is initially reduced although still present in the R7 precursor and persists in the EQC into which it develops. The EQC in wild type never expresses lacZ in H214. This result is in contrast to that seen with other enhancer trap lines that display expression in R7, and indicates that some aspect of R7 differentiation is independent of the genetic pathway(s) involving sevenless, boss and sina.

Animals↗

Pathway recognition by neuronal growth cones: genetic analysis of neural cell adhesion molecules in Drosophila.

Genetic analysis has finally come of age in the study of neural cell adhesion molecules and their function during growth cone guidance in Drosophila. Recent studies have shown that fasciclin II, a neural cell adhesion molecule of the immunoglobulin superfamily, functions as a recognition molecule for the MP1 axon pathway, thus serving as the first molecular confirmation for the existence of functional labels on specific axon pathways in the developing organism.

Animals↗

Dynamic expression of the cell adhesion molecule fasciclin I during embryonic development in Drosophila.

A number of different cell surface glycoproteins expressed in the central nervous system (CNS) have been identified in insects and shown to mediate cell adhesion in tissue culture systems. The fasciclin I protein is expressed on a subset of CNS axon pathways in both grasshopper and Drosophila. It consists of four homologous 150-amino acid domains which are unrelated to other sequences in the current databases, and is tethered to the cell surface by a glycosyl-phosphatidylinositol linkage. In this paper we examine in detail the expression of fasciclin I mRNA and protein during Drosophila embryonic development. We find that fasciclin I is expressed in several distinct patterns at different stages of development. In blastoderm embryos it is briefly localized in a graded pattern. During the germ band extended period its expression evolves through two distinct phases. Fasciclin I mRNA and protein are initially localized in a 14-stripe pattern which corresponds to segmentally repeated patches of neuroepithelial cells and neuroblasts. Expression then becomes confined to CNS and peripheral sensory (PNS) neurons. Fasciclin I is expressed on all PNS neurons, and this expression is stably maintained for several hours. In the CNS, fasciclin I is initially expressed on all commissural axons, but then becomes restricted to specific axon bundles. The early commissural expression pattern is not observed in grasshopper embryos, but the later bundle-specific pattern is very similar to that seen in grasshopper. The existence of an initial phase of expression on all commissural bundles helps to explain the loss-of-commissures phenotype of embryos lacking expression of both fasciclin I and of the D-abl tyrosine kinase. Fasciclin I is also expressed in several nonneural tissues in the embryo.

Animals↗

The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily.

Recessive lethal mutations in the fat locus of Drosophila cause hyperplastic, tumor-like overgrowth of larval imaginal discs, defects in differentiation and morphogenesis, and death during the pupal stage. Clones of mutant cells induced by mitotic recombination demonstrate that the overgrowth phenotype is cell autonomous. Here we show that the fat locus encodes a novel member of the cadherin gene superfamily: an enormous transmembrane protein of over 5000 amino acids with a putative signal sequence, 34 tandem cadherin domains, four EGF-like repeats, a transmembrane domain, and a novel cytoplasmic domain. Two recessive lethal alleles contain alterations in the fat coding sequence, and the dominant fat allele, Gull, contains an insertion of a transposable element in the 33rd cadherin domain. Thus, this novel member of the cadherin gene superfamily functions as a tumor suppressor gene and is required for correct morphogenesis.

Alleles↗

Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule.

fasiclin II (fas II), a member of the immunoglobulin superfamily, was previously characterized and cloned in grasshopper. To analyze the function of this molecule, we cloned the Drosophila fas II homolog and generated mutants in the gene. In both grasshopper and Drosophila, fasciclin II is expressed on the MP1 fascicle and a subset of other axon pathways. In fas II mutant Drosophila embryos, the CNS displays no gross phenotype, but the MP1 fascicle fails to develop. The MP1, dMP2, and vMP2 growth cones fail to recognize one another or other axons that normally join the MP1 pathway. During their normal period of axon out-growth, these growth cones stall and do not join any other neighboring pathway. Thus, fasciclin II functions as a neuronal recognition molecule for the MP1 axon pathway. These studies serve as molecular confirmation for the existence of functional labels on specific axon pathways in the developing nervous system.

Amino Acid Sequence↗