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A Ferrús

Publications and source records attributed to A Ferrús.

32 records · Page 2Linked to original sources

The behaving brain of a fly.

The use of Drosophila as a suitable system to answer behavioural questions is usually based on the availability of mutant phenotypes. Indeed, the 'single-gene' approach to behaviour was a very illuminating strategy in practical and conceptual terms, and served to prove that the genetic mechanisms sustaining behaviour could be analysed. However, the essence of neurogenetics goes for beyond the utilitarian use of mutants as tools to dissect behavior. Our main contention is that the study of the genetic basis of behaviour requires the study of genomes, rather than single genes, and their functional organization. Here, we use two aspects of behaviour, olfaction and movement control, as examples to illustrate the intricate, albeit understandable, relationship between the genome and behaviour. At present, these examples offer only a glimpse into this relationship. Further progress might be reached if studies on the regulation of functionally related genes are undertaken. On these grounds, it appears that the answer to many fundamental questions about behaviour that are amendable to experimentation might come from the work on Drosophila, providing that the required multidisciplinary efforts are focused on this organism.

Animals↗

Plasticity of motor nerve terminals in Drosophila T (X,Y)V7 mutant: effect of deregulation of the novel calcium-binding protein frequenin.

The Drosophila T(X,Y)V7 mutant is characterized by abnormally large motor responses that build up upon repetitive stimulation. Genetically it is characterized by a chromosomal breakpoint located at the proximal end of the Shaker gene complex. This mutation affects a gene which encodes a novel calcium-binding protein: the frequenin. Since neuronal activity is known to affect neurite elongation we looked for the geometry of motor terminal arborization in this mutant. Our results show a significant reduction in number and length of motor terminal branches in mutants as compared to wild type. This observation is opposite to the effect of other hyperexcitable mutations such as Shaker or ether-a-gogo or Hyperkinetic. Thus the V7 phenotype cannot be interpreted as a result of changes in motoneuron firing pattern. According to results obtained on transformed larvae in which frequenin cDNA expression was under the control of a heat shock promoter, it appears that the morphological phenotype of V7 may be due to specific effects of deregulation of this calcium-binding protein.

Animals↗

Abnormal muscle development in the heldup3 mutant of Drosophila melanogaster is caused by a splicing defect affecting selected troponin I isoforms.

The troponin I (TnI) gene of Drosophila melanogaster encodes a family of 10 isoforms resulting from the differential splicing of 13 exons. Four of these exons (6a1, 6a2, 6b1, and 6b2) are mutually exclusive and very similar in sequence. TnI isoforms show qualitative specificity whereby each muscle expresses a selected repertoire of them. In addition, TnI isoforms show quantitative specificity whereby each muscle expresses characteristic amounts of each isoform. In the mutant heldup3, the development of the thoracic muscles DLM, DVM, and TDT is aborted. The mutation consists of a one-nucleotide displacement of the 3' AG splice site at the intron preceding exon 6b1, resulting in the failure to produce all exon 6b1-containing TnI isoforms. These molecular changes in a constituent of the thin filaments cause the selective failure to develop the DLM, DVM, and TDT muscles while having no visible effect on other muscles wherein exon 6b1 expression is minor.

Amino Acid Sequence↗

Troponin I is encoded in the haplolethal region of the Shaker gene complex of Drosophila.

We have analyzed one of the nine complementation groups that constitute the haplolethal (HL) region of the Shaker gene complex (ShC). Five mutations, including a dominant lethal, define this complementation group: HL I. Mutant phenotypes show abnormal embryogenesis with structural defects in the nervous system and aberrant degeneration of specific adult muscles in addition to altered action potentials. HL I encodes a family of proteins with extensive homology to invertebrate troponin I (TnI). Members of this family are brought about by two alternative and two mutually exclusive exons in conjunction with two differential polyadenylation sites. Transcription analysis indicates that some isoforms are adult specific and others are synthesized throughout development, except during early metamorphosis. Certain isoforms of Drosophila TnI are expressed in specific muscles. The specificity of mutant phenotypes suggests a functional role of particular TnI isoforms in the development and the mature activity of muscle and nervous systems.

Amino Acid Sequence↗

Nerve terminal excitability and neuromuscular transmission in T(X;Y)V7 and Shaker mutants of Drosophila melanogaster.

We investigated the neuromuscular transmission in relation with genetic neuronal excitability changes in mutants T(X;Y)V7 and ShK,S133 of Drosophila. These mutations affect two different genes belonging to the Shaker gene complex which encode different yet functionally related proteins. Experiments were performed on neuromuscular junctions from Drosophila larvae by recording pre- and postsynaptic membrane currents using external electrodes. It was found that the neuromuscular electrophysiological phenotype of T(X;Y)V7 is caused by presynaptic membrane hyperexcitability probably in relation with a Ca2(+)-dependent down regulation of voltage dependent K channels. By contrast, the ShKS133 phenotype can be explained solely by action potential widening due to the absence of type-A K channels.

Animals↗

Genetic analysis of the Shaker gene complex of Drosophila melanogaster.

The Shaker complex (ShC) spans over 350 kb in the 16F region of the X chromosome. It can be dissected by means of aneuploids into three main sections: the maternal effect (ME), the viable (V) and the haplolethal (HL) regions. The mutational analysis of ShC shows a high density of antimorphic mutations among 12 lethal complementation groups in addition to 14 viable alleles. The complex is the structural locus of a family of potassium channels as well as a number of functions relevant to the biology of the nervous system. The constituents of ShC seem to be linked by functional relationships in view of the similarity of the phenotypes, antimorphic nature of their mutations and the behavior in transheterozygotes. We discuss the relationship between the genetic organization of ShC and the functional coupling of potassium currents with the other functions encoded in the complex.

Action Potentials↗

Antibodies against Drosophila potassium channels identify membrane proteins across species.

Shaker is a complex locus (ShC) in Drosophila that encodes components of the K+ channel responsible for the IA current. We have raised antibodies against synthetic peptides of selected sequences from the Sh products. One of the antisera identifies a 71 kDa protein band in immunoblots from Drosophila neural membrane proteins. We demonstrate that this protein is encoded within the viable (V) region of the ShC since deletions and breakpoints in this part of the complex eliminate this band from the immunoblots. Certain Sh mutations abolish the production of this product while other do not seem to interfere with it. The same antiserum identifies bands of different apparent molecular weight (Mr) in membrane extracts of nervous systems of a variety of organisms including vertebrates.

Animals↗

Genetic analysis of muscle development in Drosophila melanogaster.

The different thoracic muscles of Drosophila are affected specifically in the mutants: stripe (sr), erect wing (ewg), vertical wings (vtw), and nonjumper (nj). We have tested the extent of this specificity by means of a genetic analysis of these loci, multiple mutant combinations, and gene dosage experiments. A quantitative, rather than a qualitative, specificity is found in the mutant phenotypes. All muscles are altered by mutations in any given gene, but the severity of these alterations is muscle specific. The locus stripe seems to have a polar organization where different allelic combinations show quantitative specificity in the muscle affected. In addition to the muscle phenotypes, neural alterations are detected in these mutants. The synergism found between ewg, vtw and ewg, sr as well as the dosage effect of the distal end of the X chromosome upon the expression of ewg and sr suggests the existence of functional relationships among the loci analyzed.

Alleles↗

The expression of Ultrabithorax (Ubx) during development of the nervous system of Drosophila.

Using a double-staining technique with the neuron-specific monoclonal antibody 22C10 and the anti-Ubx monoclonal antibody FP 3-38 we describe the development of landmark cells in the nervous system of Drosophila. The staining with MAb 22C10 provides an internal system of reference that allows a precise localization of the most prominent Ubx active cells. The expression of Ubx seems to initiate at the segmental border in the hypoderm and the homologous region in the neuromeres. Also, the extent of Ubx expression follows quantitative and qualitative changes during embryonic development.

Animals↗

The pattern of early neuronal differentiation in Drosophila melanogaster.

Based on the staining of Drosophila embryos with neuron-specific monoclonal antibodies we describe the differentiation of the earliest neurons in the central nervous system. The metameric array undergoes a number of changes during development that distinguish several morphological units: metameres, neuromeres and ganglia. Neural landmarks in the CNS and the periphery are identified on the bases of their developmental history, axonal projection and segment specificity. A time sequence of differentiation starting in the posterior gnathal and anterior thoracic anlage has been found.

Age Factors↗

Enkephalin-like immunoreactivity in Drosophila melanogaster.

Enkephalin-immunoreactive neurons have been identified in the central nervous system of the fruit fly Drosophila melanogaster by immunocytochemical techniques. Analyses of fly extracts by high performance liquid chromatography and radioimmunoassay show a relatively complex pattern of immunoreactive compounds. The most prominent among them has chromatographic properties similar to those of met-enkephalin from which can, however, be distinguished by high-resolution chromatographic techniques.

Animals↗

Monoclonal antibodies against the Drosophila nervous system.

A panel of 148 monoclonal antibodies directed against Drosophila neural antigens has been prepared by using mice immunized with homogenates of Drosophila tissue. Antibodies were screened immunohistochemically on cryostat sections of fly heads. A large diversity of staining patterns was observed. Some antigens were broadly distributed among tissues; others were highly specific to nerve fibers, neuropil, muscle, the tracheal system, cell nuclei, photoreceptors, or other structures. The antigens for many of the antibodies have been identified on immunoblots. Monoclonal antibodies that identify specific molecules within the nervous system should prove useful in the study of the molecular genetics of neural development.

Animals↗

[Why so many synapses?].

INTRODUCTION AND DEVELOPMENT: Synapses are the most abundant structures in the body of all animals. This number appears to be exceedingly large considering their apparent function: excite or inhibit the postsynaptic cell. In the few cases for which data are available, the number of synapses that two identified cells establish is reasonably constant between individuals although variable during development. Observations in a variety of sensory systems and animal species indicate that synapse number is important for normal physiology. Recent data from the olfactory system in Drosophila show that, if this number increases threefold, the sensitivity of perception increases up to three orders of magnitude. Similarly, the loss of perception sensitivity to a given odorant correlates with a loss of sensory synapses in selected neurons. These changes require proper regulation of the cAMP pathway. CONCLUSIONS: It seems reasonable to assume that the postsynaptic effects in the case of N versus N synapses should be different. Since the action potential parameters in the postsynaptic cell are the same in both cases, we can propose, as a working hypothesis, that the functional differences rely in the differential calcium dynamics throughout the postsynaptic dendritic branches.

Animals↗