Thesis (Ph.D)


A genetic screen for genes involved in dendrite morphogenesis of central neurons in Drosophila melanogaster

Abstract

In order to produce a functional nervous system, it is essential that neurons project synaptic terminals into particular regions of the developing nervous system, so as to make connections with appropriate pre- and postsynaptic partners. While axon targeting has been studied extensively, much less is known about how the postsynaptic dendrites grow and branch. To study dendrite morphogenesis, a mosaic loss of function screen was developed and carried out in Drosophila melanogaster for chromosomal regions required for motor neuron dendrite development. Specifically, the Mosaic Analysis with a Repressible Cell Marker (MARCM) method was modified so that individual motor neurons can be made homozygous for a defined genomic aberration in an otherwise wild-type (heterozygous) background and visualised during early larval stages. In addition, 85 defined chromosomal deficiencies were recombined individually onto FRT-carrying chromosomes to be screened for genes involved in dendrite morphogenesis. These recombinant FRT-deficiency chromosomes provided a coverage of ~64.3% of chromosome 2 (3864 annotated genes). After analysis of ~35% of chromosome 2 (2092 annotated genes), 814 central nervous systems and 414 neurons, five genomic regions were identified that had a dendritic phenotype when absent. One of these regions, 2R:23D2;23E, uncovered by FRT40A Df(2L)S2590, was studied in more detail. Overlapping deficiencies were screened to define more precisely the region of chromosome 2 where the loss of gene(s) caused a dendritic phenotype in motor neurons. Of the seven candidate genes identified in this region, only one was shown to have expression in the embryonic central nervous system – the as yet uncharacterised gene CG34393. Based on sequence comparisons, CG34393 is predicted to encode a putative Ras guanyl exchange factor. Expression data from putative homologues in other species and Drosophila genes that are expressed in a similar developmental time course suggest that CG34393 may be involved in synapse development.

Attached files

Authors

North, Annemarie

Oxford Brookes departments

Faculty of Health and Life Sciences
Department of Biological and Medical Sciences

Dates

Year: 2011


© North, Annemarie
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