Functional differences between Ultrabithorax protein isoforms in Drosophila melanogaster: evidence from elimination, substitution and ectopic expression of specific isoforms.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 979-991 ◽  
Author(s):  
V Subramaniam ◽  
H M Bomze ◽  
A J López
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Peripheral Nervous System ◽  
Mutant Allele ◽  
Stop Codon ◽  
Functional Limitation ◽  
Ectopic Expression ◽  
Protein Isoforms ◽  
Homeodomain Protein ◽  
Alternatively Spliced

Abstract The homeotic selector gene Ultrabithorax (Ubx) specifies regional identities in multiple tissues within the thorax and abdomen of Drosophila melanogaster. Ubx encodes a family of six developmentally specific homeodomain protein isoforms translated from alternatively spliced mRNAs. The mutant allele Ubx195 contains a stop codon in exon mII, one of three differential elements, and consequently produces functional UBX protein only from mRNAs of type IVa and IVb, which are expressed mainly in the central nervous system. Although it retains activity for other processes, Ubx195 behaves like a null allele with respect to development of the peripheral nervous system, indicating that UBX-IVa and IVb alone do not contribute detectable Ubx function for this tissue. The mutant allele UbxMX17 contains an inversion of exon mII. We find that this allele only produces mRNAs of type IVa, but the expression pattern of the resulting UBX-IVa protein is indistinguishable from that of total UBX protein expression in wild-type embryos. The phenotype of homozygous UbxMX17 embryos indicates that UBX-IVa cannot substitute functionally for other isoforms to promote normal development of the peripheral nervous system. This functional limitation is confirmed by a detailed analysis of the peripheral nervous system in embryos that express specific UBX isoforms ectopically under control of a heat shock promoter. Additional observations suggest that UBX isoforms also differ in their ability to function in other tissues.

scholarly journals Loss-of-function in IRF2BPL is associated with neurological phenotypes

2018 ◽  
Author(s):  
Paul C. Marcogliese ◽  
Vandana Shashi ◽  
Rebecca C. Spillmann ◽  
Nicholas Stong ◽  
Jill A. Rosenfeld ◽  
...  
Keyword(s):  
Nervous System ◽  
Population Genomics ◽  
Stop Codon ◽  
Ectopic Expression ◽  
Premature Stop Codon ◽  
Model Organism ◽  
Global Developmental Delay ◽  
Mendelian Disease ◽  
Loss Of Function ◽  
Missense Variants

AbstractThe Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) gene encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals affected with neurological symptoms who carry damaging heterozygous variants in IRF2BPL. Five cases carrying nonsense variants in IRF2BPL resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The bioinformatics signature for IRF2BPL based on population genomics is consistent with a gene that is intolerant to variation. We show that the IRF2BPL ortholog in the fruit fly, called pits (protein interacting with Ttk69 and Sin3A), is broadly expressed including the nervous system. Complete loss of pits is lethal early in development, whereas partial knock-down with RNA interference in neurons leads to neurodegeneration, revealing requirement for this gene in proper neuronal function and maintenance. The nonsense variants in IRF2BPL identified in patients behave as severe loss-of-function alleles in this model organism, while ectopic expression of the missense variants leads to a range of phenotypes. Taken together, IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

The mouse homeodomain protein Phox2 regulates Ncam promoter activity in concert with Cux/CDP and is a putative determinant of neurotransmitter phenotype

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 881-896 ◽  
Author(s):  
I. Valarche ◽  
J.P. Tissier-Seta ◽  
M.R. Hirsch ◽  
S. Martinez ◽  
C. Goridis ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Peripheral Nervous System ◽  
Transcriptional Activation ◽  
Promoter Activity ◽  
Regulatory Element ◽  
Homeodomain Protein ◽  
Sensory Ganglia ◽  
Homeodomain Proteins ◽  
Regulatory Cascade

Transcriptional regulation of the gene encoding the cell adhesion receptor NCAM (neural cell adhesion molecule), a putative effector molecule of a variety of morphogenetic events, is likely to involve important regulators of morphogenesis. Here we identify two mouse homeodomain proteins that bind to an upstream regulatory element in the Ncam promoter: Cux, related to Drosophila cut and human CDP, and Phox2, a novel protein with a homeodomain related to that of the Drosophila paired gene. In transient transfection experiments, Cux was found to be a strong inhibitor of Ncam promoter activity, and this inhibition could be relieved by simultaneously overexpressing Phox2. These results suggest that the Ncam gene might be a direct target of homeodomain proteins and provide a striking example of regulatory cross-talk between homeodomain proteins of different classes. Whereas the expression pattern of Cux/CDP includes many NCAM-negative sites, Phox2 expression was restricted to cells also expressing Ncam or their progenitors. The localisation data thus strongly reinforce the notion that Phox2 plays a role in transcriptional activation of Ncam in Phox2-positive cell types. In the peripheral nervous system, Phox2 was strongly expressed in all ganglia of the autonomic nervous system and more weakly in some cranial sensory ganglia, but not in the sensory ganglia of the trunk. Phox2 transcripts were detected in the primordia of sympathetic ganglia as soon as they form. Phox2 expression in the brain was confined to spatially restricted domains in the hindbrain, which correspond to the noradrenergic and adrenergic nuclei once they are identifiable. All Phox2-expressing components of the peripheral nervous system are at least transiently adrenergic or noradrenergic. In the developing brain, Phox2 was expressed at all known locations of (nor)adrenergic neurones and of their precursors. These results suggest that Phox2, in addition to regulating the NCAM gene, may be part of the regulatory cascade that controls the differentiation of neurons towards this neurotransmitter phenotype.

Homeotic genes have specific functional roles in the establishment of the Drosophila embryonic peripheral nervous system

Development ◽  
1992 ◽  
Vol 115 (1) ◽  
pp. 35-47 ◽  
Author(s):  
J.G. Heuer ◽  
T.C. Kaufman
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Spatial Patterns ◽  
Ectopic Expression ◽  
Homeotic Genes ◽  
Sensory Organs ◽  
Sex Combs Reduced ◽  
Functional Roles ◽  
Visceral Mesoderm ◽  
Control Segment

The Drosophila embryonic peripheral nervous system (PNS) contains segment-specific spatial patterns of sensory organs which derive from the ectoderm. Many studies have established that the homeotic genes of Drosophila control segment specific characteristics of the epidermis, and more recently these genes have also been shown to control gut morphogenesis through their expression in the visceral mesoderm (Tremml, G. and Bienz, M. (1989), EMBO J. 8, 2677–2685). We report here the roles of homeotic genes in establishing the spatial patterns of sensory organs in the embryonic PNS. The PNS was examined in embryos homozygous for mutations in the homeotic genes Sex combs reduced (Scr), Antennapedia (Antp), Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B) with antibodies that label specific subsets of sensory organs. Our results suggest that the homeotic genes have specific roles in establishing the correct spatial patterns of sensory organs in their normal domains of expression. In addition, we also report the effects of ectopic expression of the homeotic genes labial (lab), Deformed (Dfd), Scr, Antp or Ubx on the normal development of sensory organs in the embryonic PNS. Interestingly, while previous studies have concluded that ectopic expression of the homeotic genes Dfd, Scr and Antp has no effect on the segmental identity of the abdominal segments, our results demonstrate that this is not true. We show that ectopic expression of these genes does result in the disruption of the developing PNS in the abdomen. Our results are suggestive of a role for the homeotic gene products in regulating genes which are necessary for generating sensory progenitor cells in the developing PNS.

scholarly journals Drosophila Zic family member odd-paired is needed for adult post-ecdysis maturation

Open Biology ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 190245
Author(s):  
Eléanor Simon ◽  
Sergio Fernández de la Puebla ◽  
Isabel Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Family Member ◽  
Ectopic Expression ◽  
Functional Conservation ◽  
The Central Nervous System ◽  
Behavioural Sequence

Specific neuropeptides regulate in arthropods the shedding of the old cuticle (ecdysis) followed by maturation of the new cuticle. In Drosophila melanogaster , the last ecdysis occurs at eclosion from the pupal case, with a post-eclosion behavioural sequence that leads to wing extension, cuticle stretching and tanning. These events are highly stereotyped and are controlled by a subset of crustacean cardioactive peptide (CCAP) neurons through the expression of the neuropeptide Bursicon (Burs). We have studied the role of the transcription factor Odd-paired (Opa) during the post-eclosion period. We report that opa is expressed in the CCAP neurons of the central nervous system during various steps of the ecdysis process and in peripheral CCAP neurons innerving the larval muscles involved in adult ecdysis. We show that its downregulation alters Burs expression in the CCAP neurons. Ectopic expression of Opa, or the vertebrate homologue Zic2 , in the CCAP neurons also affects Burs expression, indicating an evolutionary functional conservation. Finally, our results show that, independently of its role in Burs regulation, Opa prevents death of CCAP neurons during larval development.

scholarly journals Neurite extension of chicken peripheral nervous system neurons on fibronectin: relative importance of specific adhesion sites in the central cell-binding domain and the alternatively spliced type III connecting segment.

1988 ◽  
Vol 106 (4) ◽  
pp. 1289-1297 ◽  
Author(s):  
M J Humphries ◽  
S K Akiyama ◽  
A Komoriya ◽  
K Olden ◽  
K M Yamada
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Neurite Outgrowth ◽  
Peripheral Nervous System ◽  
Binding Domain ◽  
Central Cell ◽  
Cell Binding ◽  
Alternatively Spliced ◽  
Cell Binding Domain ◽  
Iiics Region

Fibronectin contains at least two domains that support cell adhesion. One is the central cell-binding domain that is recognized by a variety of cell types, including fibroblasts. The second, originally identified by its ability to support melanoma cell adhesion, is located in the alternatively spliced type III connecting segment (IIICS). Using specific adhesive ligands and inhibitory probes, we have examined the role of each of these domains in fibronectin-mediated neurite extension of neurons from chick embryo dorsal root and sympathetic ganglia. In studies using explanted ganglia, both fl3, a 75-kD tryptic fragment of human plasma fibronectin containing the central cell-binding domain, and CS1-IgG, a synthetic peptide-IgG conjugate containing the principal cell adhesion site from the IIICS, supported neurite outgrowth after adsorption onto the substrate. The maximal activities of fl3 and CSl-IgG were 45-55% and 25-30% that of intact fibronectin, respectively. Co-coating of the substrate with f13 and CS1-IgG produced an additive stimulation of neurite outgrowth, the extent of which approached that obtained with fibronectin. Similar results were obtained with purified neuronal cell preparations isolated by tryptic dissociation of dorsal root ganglia. In complementary studies, blockage of the adhesive function of either the central cell-binding domain (with mAb 333, an antiadhesive monoclonal antibody) or the IIICS (with CS1 peptide), resulted in approximately 60 or 30% reduction in fibronectin-mediated neurite outgrowth, respectively. When tested in combination, the inhibitory activities of mAb 333 and CSl were additive. From these results, we conclude that neurons from the peripheral nervous system can extend neurites on both the central cell-binding domain and the IIICS region of fibronectin, and that these cells are therefore the first normal, embryonic cell type shown to adhere to the IIICS. These results suggest that spatiotemporal fluctuations in the alternative mRNA splicing of the IIICS region of fibronectin may be important in regulation of cell adhesive events during development of the peripheral nervous system.

Glide directs glial fate commitment and cell fate switch between neurones and glia

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 131-139 ◽  
Author(s):  
S. Vincent ◽  
J.L. Vonesch ◽  
A. Giangrande
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Peripheral Nervous System ◽  
Glial Cell ◽  
Cell Fate ◽  
Glial Cells ◽  
Neuronal Development ◽  
Precursor Cells ◽  
A Cell ◽  
Glial Fate

Glial cells constitute the second component of the nervous system and are important during neuronal development. In this paper we describe a gene, glial cell deficient, (glide), that is necessary for glial cell fate commitment in Drosophila melanogaster. Mutations at the glide locus prevent glial cell determination in the embryonic central and peripheral nervous system. Moreover, we show that the absence of glial cells is the consequence of a cell fate switch from glia to neurones. This suggests the existence of a multipotent precursor cells in the nervous system. glide mutants also display defects in axonal navigation, which confirms and extends previous results indicating a role for glial cells in these processes.

Homologous patterns in the embryonic development of the peripheral nervous system in the grasshopper Schistocerca gregaria and the fly Drosophila melanogaster

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 241-253 ◽  
Author(s):  
T. Meier ◽  
F. Chabaud ◽  
H. Reichert
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Embryonic Development ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Schistocerca Gregaria ◽  
Spatiotemporal Pattern ◽  
Developmental Mechanisms ◽  
Pioneer Neurons ◽  
Sensory Structures

To determine the generality of developmental mechanisms involved in the construction of the insect nervous system, the embryonic development of the peripheral nervous system in the grasshopper Schistocerca gregaria was characterized at the level of identified neurons and nerve branches and then compared to that previously described from the fly Drosophila melanogaster. For this, immunocytochemistry using a neuron-specific antibody was carried out on staged grasshopper embryos. Our results show that initially a simple peripheral nerve scaffolding is established in each segment of the animal. This scaffolding consists of a pair of intersegmental nerves that are formed by identified afferent and efferent pioneer neurons and a pair of segmental nerves that are formed by afferent pioneers situated in limb buds. Subsequently, identified sets of sensory neurons differentiate in a stereotyped spatiotemporal pattern in dorsal, lateral and ventral clusters in each segment and project their axons onto these nerves. Although segment-specific differences exist, serial homologs of the developing nerves and sensory neurons can be identified. A comparison of these results with those obtained from Drosophila shows that virtually the same pattern of peripheral nerves and sensory structures is formed in both species. This indicates that the construction of the peripheral nervous system in extremely divergent modern insects relies on conserved developmental mechanisms that evolved in ancestral insects over 300 million years ago.

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