No abstract

Passover (Pas) flies fail to jump in response to a light-off stimulus. The mutation disrupts specific synapses of the giant fibers (GFs), command neurons for this response. Pas was cloned from a P element-induced allele. The cDNA encodes a putative membrane protein of 361 amino acids. Null, hypomorphic, and dominant alleles were sequenced. In the adult central nervous system, and in the pupa during GF synapse formation, Pas is consistently expressed in the GF and in a large thoracic cell in the location of its postsynaptic targets. Pas establishes a new gene family. The Drosophila ogre protein, required for postembryonic neuroblast development, is 47% identical; the C. elegans Unc-7 protein, which when mutated alters the connectivity of a few neurons, is 33% identical.

Primary ciliary dyskinesia syndrome is characterised by chronic sinusitis, bronchiectasis, and, in 50% of cases, dextrocardia. It is generally believed to be inherited as an autosomal recessive disorder. In this report, we describe a family consisting of a mother and her five male children, the offspring of three different fathers, all of whom have this syndrome. This argues for either an X linked or autosomal dominant pattern of inheritance. Cytogenetic and FISH (fluorescent in situ hybridisation) analyses were done on the mother and one son and were found to be normal.

T-cell precursors were stimulated with a conventional T-cell mitogen or with the calcium ionophore A23187 in order to determine whether pre-T cells acquire the ability to produce interleukin 2 (IL-2) before they acquire the ability to respond to antigen or mitogenic lectins. Immature T cells were obtained by eliminating mouse thymocytes that expressed the Lyt2 and L3T4 cell surface proteins. The remaining Lyt2-, L3T4- cells were stimulated for IL-2 production by using concanavalin A (Con A) or A23187, together with phorbol 12-myristate 13-acetate (PMA). We found that these "double-negative" thymocytes were unresponsive to Con A plus PMA but produced substantial amounts of IL-2 when stimulated with A23187 plus PMA. In contrast, both stimulation regimens induced more mature T-lymphocyte populations to produce IL-2. This implies that developing T cells acquire the ability to make IL-2 upon induction before they acquire the ability to be triggered by Con A. Day-15 fetal and cortical thymocytes were also tested for their ability to make IL-2. Both populations failed to synthesize this growth factor, even when stimulated with A23187 and PMA. For cortical thymocytes, this result, together with the finding that A23187 plus PMA fails to activate these cells, suggests that this population is immunologically inert rather than immature. On the other hand, the inability of day-15 fetal thymocytes to produce IL-2 indicates that these T-cell precursors are developmentally distinct from adult Lyt2-, L3T4- thymocytes, which they phenotypically resemble.

The only demonstrated mechanism for intracistronic genetic complementation requires physical interaction of A mechanism for this phenomenon was elucidated through the work of Garen and Garen (2) and Schlesinger and Levinthal (3). They studied alkaline phosphatase, an enzyme that is composed of two identical subunits (4). In studies of the phoA cistron of Escherichia coli, they showed that complementation could occur, in vivo and in vitro, when heterodimers formed between two different mutation polypeptide chains. In specific pairs of polypeptides, the heterodimer functioned at wild-type levels even though homodimers of each polypeptide were individually mutant. The mechanism for this is that different mutant subunits of a homomultimer compensate for each other and thereby give rise to a functional complex (5, 6). Subsequently, all examples of intracistronic complementation have been shown to involve such a mechanism. While the mutations studied in alkaline phosphatase were missense mutations, deletion mutations are also capable of such complementation, as in the case of the enzyme ,B-galactosidase (7).In this report, we present evidence for a different mechanism of intracistronic complementation in the Passover (Pas) locus ofDrosophila melanogaster. Pas disrupts specific synaptic connections in the neural circuit underlying the escape response of Drosophila (8). A light-off visual startle stimulus (9) or a shock to the brain (10) initiates the escape response. This reflex is mediated by the giant fiber system (GFS; see Fig. IA), eight neurons that relay excitation from the eyes to the muscles of the thorax (10). The GF axons pass from the brain to the mesothorax, where they synapse with the peripherally synapsing interneuron (PSI) and the motoneuron of the jump muscle (TTM; tergotrochanteral motoneuron). The PSI synapses with the five motoneurons of the wing depressor muscles (DLMs; dorsal longitudinal motoneurons). A single shock activation of the GF elicits a single spike in the TTM and spikes in each of the DLM fibers, resulting in a jump and initial activation of the wings.Pas flies fail to jump in response to a light-off stimulus. All the neurons are present but brain stimulation elicits no response from the DLMs and only a delayed and intermittent response from the TTM. The defect does not lie in the motor axons, neuromuscular junctions, or muscles; in Pas flies the muscles respond normally to direct stimulation of the motoneurons. Therefore, the abnormalities are in the synapses between the GF and the motoneurons it activates.Molecular cloning of the Pas locus (11) showed that Pas is expressed specifically in the GFs and its postsynaptic targets in pupae and adults. The protein product is similar to the products of the Drosophila 1(1) optic ganglion reduced (ogre) gene (12) and the Caenorhabditis elegans unc-7 gene (13). Mutations of unc-7 cause kinking during locomotion. Reconstruction of electron microscope serial sections shows that the connectivity of a premotor interneuron is altered. This ...