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1.
Biol Open ; 4(9): 1132-42, 2015 Aug 14.
Article in English | MEDLINE | ID: mdl-26276099

ABSTRACT

During development, HOX genes play critical roles in the establishment of segmental differences. In the Drosophila central nervous system, these differences are manifested in the number and type of neurons generated by each neuroblast in each segment. HOX genes can act either in neuroblasts or in postmitotic cells, and either early or late in a lineage. Additionally, they can be continuously required during development or just at a specific stage. Moreover, these features are generally segment-specific. Lately, it has been shown that contrary to what happens in other tissues, where HOX genes define domains of expression, these genes are expressed in individual cells as part of the combinatorial codes involved in cell type specification. In this report we analyse the role of the Bithorax-complex genes - Ultrabithorax, abdominal-A and Abdominal-B - in sculpting the pattern of crustacean cardioactive peptide (CCAP)-expressing neurons. These neurons are widespread in invertebrates, express CCAP, Bursicon and MIP neuropeptides and play major roles in controlling ecdysis. There are two types of CCAP neuron: interneurons and efferent neurons. Our results indicate that Ultrabithorax and Abdominal-A are not necessary for specification of the CCAP-interneurons, but are absolutely required to prevent the death by apoptosis of the CCAP-efferent neurons. Furthermore, Abdominal-B controls by repression the temporal onset of neuropeptide expression in a subset of CCAP-efferent neurons, and a peak of ecdysone hormone at the end of larval life counteracts this repression. Thus, Bithorax complex genes control the developmental appearance of these neuropeptides both temporally and spatially.

2.
Genes Dev ; 12(18): 2912-20, 1998 Sep 15.
Article in English | MEDLINE | ID: mdl-9744867

ABSTRACT

Formation of the dorsal-ventral axis of the Drosophila wing depends on activity of the LIM-homeodomain protein Apterous (Ap). Here we report that Ap activity levels are modulated by dLMO, the protein encoded by the Beadex (Bx) gene. Overexpression of dLMO in Bx mutants interferes with Apterous function. Conversely, Bx loss-of-function mutants fail to down-regulate Apterous activity at late stages of wing development. Biochemical analysis shows that dLMO protein competes for binding of Apterous to its cofactor Chip. These data suggest that Apterous activity depends on formation of a functional complex with Chip and that the relative levels of dLMO, Apterous, and Chip determine the level of Apterous activity. The dominant interference mechanism of dLMO action may serve as a model for the mechanism by which LMO oncogenes cause cancer when misexpressed in T cells.


Subject(s)
Drosophila Proteins , Drosophila/growth & development , Drosophila/genetics , Genes, Insect , Homeodomain Proteins/genetics , Homeodomain Proteins/physiology , Transcription Factors/physiology , Animals , Base Sequence , DNA Primers/genetics , Drosophila/physiology , Gene Expression Regulation, Developmental , Genes, Homeobox , In Situ Hybridization , Insect Proteins/physiology , LIM-Homeodomain Proteins , Macromolecular Substances , Models, Biological , Molecular Sequence Data , Mutagenesis, Insertional , Nuclear Proteins/physiology , Oncogenes , Phenotype , Polymerase Chain Reaction , Wings, Animal/growth & development
3.
Nature ; 381(6580): 316-8, 1996 May 23.
Article in English | MEDLINE | ID: mdl-8692268

ABSTRACT

Limb development in Drosophila depends on subdivision of the limb primordia into functional units called compartments. Cell interactions across compartment boundaries establish pattern-organizing centres that control growth and specify cell fates along the anteroposterior (AP) and dorsoventral (DV) axes of the limbs. AP subdivision of the disc primordia is inherited from the embryonic ectoderm. DV subdivision of the wing disc occurs during the second larval instar through localized expression of the apterous protein (Apterous) in dorsal cells. A third major subdivision of the wing disc into wing and body-wall compartments also occurs in the second instar. Here we show that specification of the wing primordium in early second instar depends on activity of the AP patterning system but not the DV system. These results define two distinct roles for the wingless gene: a primary role in specifying the wing primordium, and a subsequent role mediating the patterning activities of the DV compartment boundary.


Subject(s)
Drosophila Proteins , Drosophila/embryology , Proto-Oncogene Proteins/physiology , Wings, Animal/embryology , Animals , Drosophila/cytology , Drosophila/genetics , Morphogenesis/physiology , Mutation , Proto-Oncogene Proteins/genetics , Wings, Animal/cytology , Wnt1 Protein
4.
Annu Rev Cell Dev Biol ; 12: 161-80, 1996.
Article in English | MEDLINE | ID: mdl-8970725

ABSTRACT

Recent studies on the development of the legs and wings of Drosophila have led to the conclusion that insect limb development is controlled by localized pattern organizing centers, analogous to those identified in vertebrate embryos. Genetic analysis has defined the events that lead to the formation of these organizing centers and has led to the identification of gene products that mediate organizer function. The possibility of homology between vertebrate and insect limbs is considered in light of recently reported similarities in patterns of gene expression and function.


Subject(s)
Extremities/embryology , Gene Expression Regulation, Developmental , Animals , Drosophila/embryology , Drosophila/genetics , Vertebrates/embryology
5.
Development ; 121(12): 4215-25, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8575321

ABSTRACT

Growth and patterning of the Drosophila wing is controlled by organizing centers located at the anterior-posterior and dorsal-ventral compartment boundaries. Interaction between cells in adjacent compartments establish the organizer. We report here that Serrate and Notch mediate the interaction between dorsal and ventral cells to direct localized expression of Wingless at the D/V boundary. Serrate serves as a spatially localized ligand which directs Wg expression through activation of Notch. Ligand independent activation of Notch is sufficient to direct Wg expression, which in turn mediates the organizing activity of the D/V boundary.


Subject(s)
Drosophila Proteins , Drosophila/embryology , Embryonic Induction/genetics , Genes, Insect , Membrane Proteins/genetics , Proto-Oncogene Proteins/genetics , Wings, Animal/embryology , Animals , Calcium-Binding Proteins , Drosophila/genetics , Gene Expression , Intercellular Signaling Peptides and Proteins , Jagged-1 Protein , Models, Biological , Morphogenesis , Receptors, Notch , Serrate-Jagged Proteins , Wnt1 Protein
6.
Nature ; 373(6516): 711-5, 1995 Feb 23.
Article in English | MEDLINE | ID: mdl-7854456

ABSTRACT

Interaction between distinctly specified cells in adjacent compartments establishes organizing centres that control growth and specify cell fate in the developing limbs of Drosophila. Localized expression of the secreted Hedgehog protein (Hh) by cells in the posterior compartment induces expression of the secreted signalling molecules decapentaplegic (dpp) or wingless (wg) in nearby anterior cells. wg and dpp in turn organize spatial pattern in the wing and leg imaginal discs. The Hh signal is thought to act by antagonizing the ability of the patched (ptc) gene product to repress wg and dpp expression. Here we present evidence that removing activity of the gene encoding cyclic AMP-dependent protein kinase A (pka) is functionally equivalent to removing ptc activity or to providing cells with the Hh signal. These findings suggest that cyclic AMP-dependent protein kinase A is a component of the signal transduction pathway through which Hh and Ptc direct localized expression of dpp (or wg) and establish the compartment boundary organizer.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Drosophila Proteins , Drosophila/embryology , Signal Transduction , Alleles , Animals , Base Sequence , Cyclic AMP-Dependent Protein Kinases/genetics , DNA , Drosophila/enzymology , Drosophila/genetics , Extremities/embryology , Genes, Lethal , Hedgehog Proteins , Insect Hormones/physiology , Membrane Proteins/physiology , Molecular Sequence Data , Mutation , Proteins/physiology , Proto-Oncogene Proteins/physiology , Receptors, Cell Surface , Wings, Animal/embryology , Wnt1 Protein
7.
Development ; 121(2): 589-99, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7768195

ABSTRACT

The nubbin gene is required for normal growth and patterning of the wing in Drosophila. We report here that nubbin encodes a member of the POU family of transcription factors. Regulatory mutants which selectively remove nubbin expression from wing imaginal discs lead to loss of wing structures. Although nubbin is expressed throughout the wing primordium, analysis of genetic mosaics suggests a localized requirement for nubbin activity in the wing hinge. These observations suggest the existence of a novel proximal-distal growth control center in the wing hinge, which is required in addition to the well characterized anterior-posterior and dorsal-ventral compartment boundary organizing centers.


Subject(s)
Drosophila/embryology , Ectoderm/physiology , Genes, Insect , Transcription Factors/physiology , Wings, Animal/embryology , Animals , Drosophila/genetics , Gene Expression , In Situ Hybridization , Morphogenesis/genetics , Mutation , Phenotype , Transcription Factors/genetics
8.
Nature ; 372(6502): 175-9, 1994 Nov 10.
Article in English | MEDLINE | ID: mdl-7969450

ABSTRACT

The appendage primordia of Drosophila are subdivided into compartments by the localized expression of transcription factors. Interaction between cells in adjacent compartments establishes organizing centres responsible for generating spatial pattern and promoting cell proliferation in the developing appendages. Localized expression of hedgehog (hh) in the posterior compartment of the leg imaginal disc directs expression of wingless (wg) in ventral-anterior cells and decapentaplegic (dpp) in dorsal-anterior cells near the anterior-posterior compartment boundary; wg then acts to specify ventral cell fate and to organize the dorsal-ventral axis of the leg. Interaction between wg-expressing ventral cells and dorsal cells near the anterior-posterior compartment boundary promotes axis formation in the leg. Here we show that the combined action of wg-expressing cells in the ventral-anterior compartment and dpp-expressing cells in the dorsal-anterior compartment activates expression of Distal-less, a gene required for proximal-distal axis formation in the limbs. These results demonstrate that sequential interaction between anterior-posterior and dorsal-ventral compartments establishes the proximal-distal axis of the limbs.


Subject(s)
Drosophila Proteins , Drosophila/growth & development , Insect Hormones/physiology , Proteins/physiology , Proto-Oncogene Proteins/physiology , Animals , Extremities/growth & development , Gene Expression Regulation, Developmental/physiology , Genes, Homeobox/physiology , Hedgehog Proteins , Homeodomain Proteins/biosynthesis , Larva/growth & development , Wnt1 Protein
9.
Development ; 120(6): 1661-70, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8050372

ABSTRACT

The secreted glycoproteins encoded by Wnt genes are thought to function as intercellular signaling molecules which convey positional information. Localized expression of Wingless protein is required to specify the fate of ventral cells in the developing Drosophila leg. We report here that Wingless acts through inactivation of the shaggy/zeste white 3 protein kinase to specify ventral cell fate in the leg. Ectopic expression of Wingless outside its normal ventral domain has been shown reorganize the dorsal-ventral axis of the leg in a non-autonomous manner. Using genetic mosaics, we show that cells that lack shaggy/zeste white 3 activity can influence the fate of neighboring cells to reorganize dorsal-ventral pattern in the leg, in the same manner as Wingless-expressing cells. Therefore, clones of cells that lack shaggy/zeste white 3 activity exhibit all of the organizer activity previously attributed to Wingless-expressing cells, but do so without expressing wingless. We also show that the organizing activity of ventral cells depends upon the location of the clone along the dorsal-ventral axis. These findings suggest that Wingless protein does not function as a morphogen in the dorsal-ventral axis of the leg.


Subject(s)
Drosophila Proteins , Drosophila/genetics , Embryonic Induction/physiology , Extremities/embryology , Genes, Insect/physiology , Glycogen Synthase Kinase 3 , Protein Kinases/physiology , Animals , Drosophila/embryology , Ectoderm/physiology , Immunohistochemistry , Morphogenesis/genetics , Mosaicism
10.
Development ; 120(3): 569-78, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8162856

ABSTRACT

In Drosophila, Drk, an SH2 adaptor protein, Sos, a putative activator of Ras1, Ras1, raf and rolled/MAP kinase have been shown to be required for signalling from the sevenless and the torso receptor tyrosine kinase. From these studies, it was unclear whether these components act in a single linear pathway as suggested by the genetic analysis or whether different components serve to integrate different signals. We have analyzed the effects of removing each of these components during the development of the adult epidermal structures by generating clones of homozygous mutant cells in a heterozygous background. Mutations in each of these signalling components produce a very similar set of phenotypes. These phenotypes resemble those caused by loss-of-function mutations in the Drosophila EGF receptor homolog (DER). It appears that these components form a signalling cassette, which mediates all aspects of DER signalling but that is not required for other signalling processes during epidermal development.


Subject(s)
Drosophila Proteins , Drosophila/genetics , Epidermis/embryology , ErbB Receptors/physiology , Eye Proteins/genetics , Genes, Insect/genetics , Membrane Glycoproteins/genetics , Receptor Protein-Tyrosine Kinases , Signal Transduction/genetics , Wings, Animal/embryology , Animals , Cell Differentiation/genetics , Drosophila/embryology , Morphogenesis/genetics , Mutation/genetics , Phenotype
11.
Cell ; 75(4): 741-52, 1993 Nov 19.
Article in English | MEDLINE | ID: mdl-8242746

ABSTRACT

The adult appendages of Drosophila develop from imaginal discs. An early step in disc patterning involves the formation of developmental boundaries that subdivide the discs into compartments. Anterior and posterior compartments are established in the embryo. Later in development a new boundary originates to subdivide the wing disc into dorsal and ventral compartments, which correspond to the dorsal and ventral surfaces of the adult wing. We report here that spatially localized expression of the homeobox gene apterous (ap) specifies the identity of dorsal cells in the wing. The boundary of cell lineage restriction between dorsal and ventral compartments coincides with the limit of the domain of ap expression. Using genetic mosaics, we show that juxtaposition of dorsal and ventral cells induces formation of the wing margin. We present evidence that the dorsal-ventral boundary promotes growth and serves as a pattern-organizing center in the wing disc.


Subject(s)
Drosophila Proteins , Drosophila melanogaster/embryology , Homeodomain Proteins , Transcription Factors/physiology , Wings, Animal/embryology , Animals , Animals, Genetically Modified , Embryonic Induction , Gene Expression , In Situ Hybridization , LIM-Homeodomain Proteins , Mutagenesis, Insertional
12.
Proc Biol Sci ; 242(1303): 36-44, 1990 Oct 22.
Article in English | MEDLINE | ID: mdl-1980740

ABSTRACT

The Drosophila homologue of the epidermal growth factor receptor (DEGFr or DER, also called torpedo or top) has many mutant alleles that cause either embryonic lethality (both early and late), pupal lethality or female sterility, possibly corresponding to degrees of hypomorphism. We have studied the clonal behaviour of some lethal alleles in genetic mosaics in the imaginal development of thorax, head and tergite epidermis. These alleles cause reduced cell viability to different degrees (measured in frequency and size of clones), smaller cell sizes, abnormal patterning of sensory-organ differentiation and lack of differentiation of macro-chaetae and veins. These effects are cell-autonomous but also cause abnormal differentiation in wild-type cells surrounding the clones. In addition, we have studied the phenotypes of double mutant combinations of viable top alleles with wing-pattern mutants, some related to other Drosophila proto-oncogenes, to reveal gene interactions in the role(s) of DER in cell proliferation and differentiation. We discuss how those complex cell-behaviour phenotypes and genetic interactions are related to the molecular nature of the DER.


Subject(s)
Drosophila/genetics , ErbB Receptors/genetics , Alleles , Animals , Cell Differentiation/genetics , Clone Cells/cytology , Drosophila/cytology , Drosophila/metabolism , Genes, Lethal , Mosaicism , Mutation , Phenotype
13.
Rouxs Arch Dev Biol ; 198(6): 336-354, 1990 Mar.
Article in English | MEDLINE | ID: mdl-28305413

ABSTRACT

Of the many mutations known to affect the wing vein pattern we have selected the most extreme in 29 genes for study. Their phenotype can be classified in two major classes: lack-of-veins and excess-of-veins, and in several internally coherent groups. The study of multiple mutant combinations, within groups and between groups, reveals several genetic operations at work in the generation of the vein pattern. The finding that some of these mutations also affect cell proliferation in characteristic ways has prompted a generative model of wing morphogenetic and pattern formation based on cell behaviour properties defined by the corresponding wild-type genes.

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