Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless.

An expressed gene sequence which was identified by the isolation of a methylation free CpG island from human chromosome 7 has been cloned from a human lung cDNA library. The deduced protein sequence contains 360 amino acids and has several features of a secreted protein; it is cysteine rich with a signal peptide sequence and two potential asn-linked glycosylation sites. The protein sequence shows marked similarity with human and murine int-1 and their Drosophila homolog wingless (Dint-1). This human int-1 related protein, int-1 and Dint-1 have diverse patterns of expression, but the inferred structural similarities suggest that some of the functional characteristics of these proteins may be shared.     

Avoiding the SCAMs

Dendrites from the same neuron usually avoid contact with one another, a behavior known as self-avoidance. In this issue of Neuron and in the upcoming May 4, 2007 issue of Cell, a pair of studies by Soba et al. and Hughes et al. and a study by Matthews et al., respectively, identify products from the highly alternatively spliced Dscam gene as central to this behavior in Drosophila. Signaling induced by adhesion between identical isoforms triggers repulsion between sister dendrites.     

Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion

The Wnt-1 gene plays an essential role in fetal brain development and encodes a secreted protein whose signaling mechanism is presently unknown. In this report we have investigated intracellular mechanisms by which the Wnt-1 gene induces morphological changes in PC12 pheochromocytoma cells. PC12 cells expressing Wnt-1 show increased steady-state levels of the adhesive junction protein plakoglobin, and an altered distribution of this protein within the cell. This effect appears similar to a modulation of the plakoglobin homolog, Armadillo, that occurs in Drosophila embryos in response to the Wnt-1 homolog, wingless (Riggleman, B., P. Schedl, and E. Wieschaus. 1990. Cell. 63:549-560). In addition, PC12/Wnt-1 cells show elevated expression of E-cadherin and increased calcium-dependent cell-cell adhesion. These results imply evolutionary conservation of cellular responses to Wnt- 1/wingless and indicate that in certain cell types Wnt-1 may act to modulate cell adhesion mechanisms.     

Two different thresholds of wingless signalling with distinct developmental consequences in the Drosophila midgut.

Drosophila wingless encodes a Wnt protein which mediates communication between cells. Although wingless protein is secreted from cells, there is debate as to what is the range of wingless action. We examined the function of wingless in the larval midgut, and found that wingless acts at two different thresholds to pattern this tissue. Low wingless levels are required to promote the development of copper cells, highly differentiated midgut cells of the larval midgut that are specified by the homeotic gene labial. High wingless levels repress copper cell development and allow differentiation of an alternative cell type, called large flat cells. These two developmental outcomes reflect labial expression, which is stimulated at low levels and repressed at high levels of wingless signalling. Thus, midgut cells respond differentially to distinct wingless thresholds in terms of both gene control and cellular differentiation.     

Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog.

The segment polarity genes engrailed and wingless are expressed in neighboring stripes of cells on opposite sides of the Drosophila parasegment boundary. Each gene is mutually required for maintenance of the other's expression; continued expression of both also requires several other segment polarity genes. We show here that one such gene, hedgehog, encodes a protein targeted to the secretory pathway and is expressed coincidently with engrailed in embryos and in imaginal discs; maintenance of the hedgehog expression pattern is itself dependent upon other segment polarity genes including engrailed and wingless. Expression of hedgehog thus functions in, and is sensitive to, positional signaling. These properties are consistent with the non-cell autonomous requirement for hedgehog in cuticular patterning and in maintenance of wingless expression.     

Embryonic and imaginal requirements for wingless, a segment-polarity gene in Drosophila

In Drosophila melanogaster mutant alleles of the segmentation gene wingless fall into two classes: winglessLethal mutations are embryonic lethals with a segment-polarity phenotype; the wingless1 mutation is viable when homozygous and produces a homeotic transformation in adults. This paper further describes the embryonic lethal phenotype, and also pole-cell transplants, experiments with a temperature-sensitive mutation, and clonal analysis with a winglessLethal mutation. It is argued that the wg gene is zygotically required after gastrulation for the normal patterning of each embryonic segment. The gene is still required in the larval stages, and the cell nonautonomy of this function supports the view that the wg gene product may be involved in intercellular signaling during development.