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Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12944-9. Epub 2005 Aug 25.

An isoform-specific allele of Drosophila N-cadherin disrupts a late step of R7 targeting.

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Department of Biological Chemistry, David Geffen School of Medicine, University of California and Howard Hughes Medical Institute, Los Angeles, CA 90095, USA.


Drosophila N-cadherin is required for the formation of precise patterns of connections in the fly brain. Alternative splicing is predicted to give rise to 12 N-cadherin isoforms. We identified an N-cadherin allele, N-cad(18Astop), that eliminates the six isoforms containing alternative exon 18A and demonstrate that it strongly disrupts the connections of R7 photoreceptor neurons. During the first half of pupal development, N-cadherin is required for R7 growth cones to terminate within a temporary target layer in the medulla. N-cadherin isoforms containing exon 18B are sufficient for this initial targeting. By contrast, 18A isoforms are preferentially expressed in R7 during the second half of pupal development and are necessary for R7 to terminate in the appropriate synaptic layer in the medulla neuropil. Transgene rescue experiments suggest that differences in isoform expression, rather than biochemical differences between isoforms, underlie the 18A isoform requirement in R7 neurons.

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