Laboratoire d' Embryologie Moleculaire, Universite Paris XI, Bat 445, 91405 Orsay Cedex, France. FAX: 33 1 69 85 35 38 .TEL: 33 1 69 41 74 65 E-mail: dura@pop.u-psud.fr ,
The linotte1 mutant was derived from a PlacW transposon mutagenesis and was screened for three-hour memory deficit after classical conditioning of an olfactory avoidance response. Sensory and motor systems (olfactory acuity and shock reactivity) required for the classical conditioning experiments were normal in mutant flies (1). Northern analysis and screening of an head cDNA library revealed that the P element is inserted between two transcriptional units. The insertion site corresponds to the 3' untranscribed region of one unit, that we have called pigeon, and of the 5' transcribed region of the other unit. Several lines of evidence show that this second unit, which is at least 17 Kb long and produces a 3.2 Kb mature RNA, corresponds to the linotte gene. The linotte gene is homologous to a human receptor tyrosine kinase. linotte individuals carrying a null mutation (a deletion of the first 4 Kbs of the linotte transcriptional unit), linotte2, are viable and show a more extreme memory defect (2). In linotte2 individuals the pigeon transcriptional unit appears unaffected as it is revealed by a 5' probe of the pigeon cDNA on adults. linotte2 individuals have clear central brain phenotypes. The central complex is distorted on its dorsal part, where abnormal axons are present and the beta/gamma lobes of the mushroom bodies are fused together at the level of the median bundle. Our working hypothesis is that these adult phenotypes are due to abnormal axonal guidance as it was shown that the lack of the LINOTTE tyrosine kinase affect neuronal pathway in the embryo (3- note that these authors have named the gene: derailed). A 28 Kb transgene bearing the genomic linotte DNA is able to rescue these brain defects. In contrast a pigeon genomic DNA transgene shows no rescue of these brain phenotypes. It seems difficult to conciliate our results with the published data of the rescue of the linotte behavioural phenotype with a transgene carrying a pigeon cDNA under a heat-shock promoter (4). Behavioural rescue experiments are currently underway and should shed much needed light on the resolution of this problem.
(1) Dura, Preat and Tully (1993) J. Neurogenet. 9, 1-14. (2) Dura, Taillebourg and Preat (1995) FEBS letters 370, 250-254. (3) Callahan, Muralidhar, Lundgren, Scully and Thomas (1995) Nature 376, 171-174. (4) Bolwig, Del Vecchio, Hannon and Tully (1995) Neuron 15, 829-842.