Guidance cues at the Drosophila CNS midline: identification and characterization of two Drosophila Netrin/UNC-6 homologs.
Netrins are chemotropic guidance signals that play important roles in circumferential axon guidance in C. elegans and in the developing vertebrate spinal cord. We have identified two Drosophila homologs of this protein family (Netrin-A and Netrin-B). Both Netrins are dynamically expressed throughout embryogenesis, including CNS midline expression at the time of commissure formation. Both Netrin genes map close to each other on the X chromosome, and embryos deficient for this region exhibit defects in commissure formation. This CNS phenotype can be rescued by expression of either Netrin at the CNS midline, confirming an important role for Drosophila Netrins in commissural growth cone guidance. A localized source of Netrin protein at the midline is apparently important for function, since ectopic expression of either Netrin throughout the CNS results in phenotypic defects similar to the loss-of-function phenotype.
Harris
R
R
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Sabatelli
L M
LM
Seeger
M A
MA
D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000502:physiology; D002871:Chromosome Banding; D002874:Chromosome Mapping; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D017344:Genes, Insect / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000737:chemistry* / Q000235:genetics*; D000075388:Netrin-1; D000075385:Netrins; D016501:Neurites / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins; D014960:X Chromosome / Q000235:genetics
D029721:Drosophila Proteins; D009414:Nerve Growth Factors; C000617352:NetA protein, Drosophila; D000075385:Netrins; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C088894:netrin-2