rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 843-851 ◽  
Author(s):  
Craig A. Micchelli ◽  
Inge The ◽  
Erica Selva ◽  
Vladic Mogila ◽  
Norbert Perrimon
Keyword(s):  
Hedgehog Signaling ◽  
Transmembrane Protein ◽  
Post Translational Modification ◽  
Protein Levels ◽  
Lethal Mutations ◽  
Segment Polarity ◽  
Invertebrate Development ◽  
Membrane Bound ◽  
Segment Polarity Gene ◽  
Polarity Gene

Members of the Hedgehog (Hh) family encode secreted molecules that act as potent organizers during vertebrate and invertebrate development. Post-translational modification regulates both the range and efficacy of Hh protein. One such modification is the acylation of the N-terminal cysteine of Hh. In a screen for zygotic lethal mutations associated with maternal effects, we have identified rasp, a novel Drosophila segment polarity gene. Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. The requirement of rasp is restricted only to those cells that produce Hh; hh transcription, protein levels and distribution are not affected by the loss of rasp. Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein.

Subcellular localization of the segment polarity protein patched suggests an interaction with the wingless reception complex in Drosophila embryos

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 987-998 ◽  
Author(s):  
J. Capdevila ◽  
F. Pariente ◽  
J. Sampedro ◽  
J.L. Alonso ◽  
I. Guerrero
Keyword(s):  
Transmembrane Protein ◽  
Cell Communication ◽  
Epidermal Cells ◽  
Communication Processes ◽  
Segment Polarity ◽  
Membrane Bound ◽  
Endocytic Vesicles ◽  
Segment Polarity Gene ◽  
Drosophila Embryos ◽  
Polarity Gene

The product of the segment polarity gene patched is a transmembrane protein involved in the cell communication processes that establish polarity within the embryonic segments of Drosophila. Monoclonal antibodies have been raised against the patched protein, and by immunoelectron microscopy part of the patched staining is found associated with discrete regions of the lateral plasma membrane of the embryonic epidermal cells. Using a mutation affecting endocytosis (shibire) we find that patched is a membrane-bound protein, which is internalized by endocytosis, and that the preferential sites of accumulation resemble the described localization of the cell-cell adhesive junctions of the epidermal cells. patched partially co-localizes with the wingless protein in the wingless-expressing and nearby cells, in structures that seem to be endocytic vesicles. These data suggest the interaction of patched protein with elements of the reception complex of wingless, as a way to control the wingless expression.

Positional signaling by hedgehog in Drosophila imaginal disc development

Development ◽  
1995 ◽  
Vol 121 (1) ◽  
pp. 1-10 ◽  
Author(s):  
A.L. Felsenfeld ◽  
J.A. Kennison
Keyword(s):  
Hedgehog Signaling ◽  
Imaginal Disc ◽  
Ectopic Expression ◽  
Posterior Compartment ◽  
Anterior Compartment ◽  
Segment Polarity ◽  
Wing Structures ◽  
Wing Discs ◽  
Segment Polarity Gene ◽  
Polarity Gene

We describe a dominant gain-of-function allele of the segment polarity gene hedgehog. This mutation causes ectopic expression of hedgehog mRNA in the anterior compartment of wing discs, leading to overgrowth of tissue in the anterior of the wing and partial duplication of distal wing structures. The posterior compartment of the wing is unaffected. Other imaginal derivatives are affected, resulting in duplications of legs and antennae and malformations of eyes. In mutant imaginal wing discs, expression of the decapentaplegic gene, which is implicated in the hedgehog signaling pathway, is also perturbed. The results suggest that hedgehog protein acts in the wing as a signal to instruct neighboring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary.

scholarly journals Mutations that alter the timing and pattern of cubitus interruptus gene expression in Drosophila melanogaster.

Genetics ◽  
1995 ◽  
Vol 139 (1) ◽  
pp. 229-240 ◽  
Author(s):  
D C Slusarski ◽  
C K Motzny ◽  
R Holmgren
Keyword(s):  
Serine Threonine Kinase ◽  
Cubitus Interruptus ◽  
Threonine Kinase ◽  
Protein Levels ◽  
Segment Polarity ◽  
Subsequent Elimination ◽  
Wing Veins ◽  
Inappropriate Expression ◽  
Segment Polarity Gene ◽  
Polarity Gene

Abstract The cubitus interruptus (ci) gene is a member of the Drosophila segment polarity gene family and encodes a protein with a zinc finger domain homologous to the vertebrate Gli genes and the nematode tra-1 gene. Three classes of existing mutations in the ci locus alter the regulation of ci expression and can be used to examine ci function during development. The first class of ci mutations causes interruptions in wing veins four and five due to inappropriate expression of the ci product in the posterior compartment of imaginal discs. The second class of mutations eliminates ci protein early in embryogenesis and causes the deletion of structures that are derived from the region including and adjacent to the engrailed expressing cells. The third class of mutations eliminates ci protein later in embryogenesis and blocks the formation of the ventral naked cuticle. The loss of ci expression at these two different stages in embryonic development correlates with the subsequent elimination of wingless expression. Adults heterozygous for the unique ciCe mutation have deletions between wing veins three and four. A similar wing defect is present in animals mutant for the segment polarity gene fused that encodes a putative serine/threonine kinase. In ciCe/+ and fused mutants, the deletions between wing veins three and four correlate with increased ci protein levels in the anterior compartment. Thus, proper regulation of both the ci mRNA and protein appears to be critical for normal Drosophila development.

Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila

Development ◽  
1992 ◽  
Vol 115 (4) ◽  
pp. 957-971 ◽  
Author(s):  
J. Mohler ◽  
K. Vani
Keyword(s):  
Transmembrane Protein ◽  
Cell Communication ◽  
Protein Product ◽  
Drosophila Embryo ◽  
Molecular Organization ◽  
Posterior Portion ◽  
Segment Polarity ◽  
Segment Polarity Gene ◽  
Polarity Gene ◽  
Cell Cell

hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication.

Transcription of the segment-polarity gene wingless in the imaginal discs of Drosophila, and the phenotype of a pupal-lethal wg mutation

Development ◽  
1988 ◽  
Vol 102 (3) ◽  
pp. 489-497 ◽  
Author(s):  
N.E. Baker
Keyword(s):  
In Situ Hybridization ◽  
Imaginal Discs ◽  
Apical Cytoplasm ◽  
Segment Polarity ◽  
Disc Cells ◽  
Segment Polarity Gene ◽  
Drosophila Embryos ◽  
Polarity Gene

Wingless (wg) is a segment-polarity gene in Drosophila which is related to the murine proto-oncogene int1. In Drosophila embryos, wg transcription defines part of each parasegment. In situ hybridization shows that wg is also expressed in the imaginal discs which give rise to the adult during metamorphosis. Transcripts are localized in the apical cytoplasm of disc cells, and accumulate in different patterns in dorsal and ventral discs. The wgCX3 mutation produces morphological defect in the adult structures derived from these imaginal discs. The results show that wg is involved in the development of the adult, as well as the embryo, but that the imaginal discs do not express this segment-polarity gene in an identical pattern to the embryonic segments.

The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1029-1043 ◽  
Author(s):  
M. Peifer ◽  
C. Rauskolb ◽  
M. Williams ◽  
B. Riggleman ◽  
E. Wieschaus
Keyword(s):  
Pattern Formation ◽  
Imaginal Discs ◽  
Protein Accumulation ◽  
Segment Polarity Genes ◽  
Adult Pattern ◽  
Segment Polarity ◽  
Lethal Allele ◽  
Segment Polarity Gene ◽  
Polarity Gene

The segment polarity genes of Drosophila were initially defined as genes required for pattern formation within each embryonic segment. Some of these genes also function to establish the pattern of the adult cuticle. We have examined the role of the armadillo (arm) gene in this latter process. We confirmed and extended earlier findings that arm and the segment polarity gene wingless are very similar in their effects on embryonic development. We next discuss the role of arm in pattern formation in the imaginal discs, as determined by using a pupal lethal allele, by analyzing clones of arm mutant tissue in imaginal discs, and by using a transposon carrying arm to produce adults with a reduced level of arm. Together, these experiments established that arm is required for the development of all imaginal discs. The requirement for arm varies along the dorsal-ventral and proximal-distal axes. Cells that require the highest levels of arm are those that express the wingless gene. Further, animals with reduced arm levels have phenotypes that resemble those of weak alleles of wingless. We present a description of the patterns of arm protein accumulation in imaginal discs. Finally, we discuss the implications of these results for the role of arm and wingless in pattern formation.

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