Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila.
Anaplastic lymphoma kinase (Alk) has been proposed to regulate neuronal development based on its expression pattern in vertebrates and invertebrates; however, its function in vivo is unknown. We demonstrate that Alk and its ligand Jelly belly (Jeb) play a central role as an anterograde signaling pathway mediating neuronal circuit assembly in the Drosophila visual system. Alk is expressed and required in target neurons in the optic lobe, whereas Jeb is primarily generated by photoreceptor axons and functions in the eye to control target selection of R1-R6 axons in the lamina and R8 axons in the medulla. Impaired Jeb/Alk function affects layer-specific expression of three cell-adhesion molecules, Dumbfounded/Kirre, Roughest/IrreC, and Flamingo, in the medulla. Moreover, loss of flamingo in target neurons causes some R8-axon targeting errors observed in Jeb and Alk mosaic animals. Together, these findings suggest that Jeb/Alk signaling helps R-cell axons to shape their environment for target recognition.
Bazigou
Eleni
E
Division of Molecular Neurobiology, MRC National Institute for Medical Research, London NW7 1AA, UK.
Apitz
Holger
H
Johansson
Jana
J
Lorén
Christina E
CE
Hirst
Elizabeth M A
EM
Chen
Pei-Ling
PL
Palmer
Ruth H
RH
Salecker
Iris
I
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D005123:Eye / Q000254:growth & development / Q000294:innervation; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D007814:Larva / Q000254:growth & development; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009899:Optic Lobe, Nonmammalian / Q000254:growth & development; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011679:Pupa / Q000254:growth & development; D020794:Receptor Protein-Tyrosine Kinases; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction
D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C440828:jeb protein, Drosophila; C413082:kirre protein, Drosophila; C085209:rst protein, Drosophila; C121420:stan protein, Drosophila; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases