An isoform-specific allele of Drosophila N-cadherin disrupts a late step of R7 targeting.
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.
Nern
Aljoscha
A
Department of Biological Chemistry, David Geffen School of Medicine, University of California and Howard Hughes Medical Institute, Los Angeles, CA 90095, USA.
Nguyen
Louis-Vu T
LV
Herman
Tory
T
Prakash
Saurabh
S
Clandinin
Thomas R
TR
Zipursky
S Lawrence
SL
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000254:growth & development / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011679:Pupa / Q000254:growth & development / Q000378:metabolism; D016415:Sequence Alignment
D015820:Cadherins; D020033:Protein Isoforms