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First published online 12 August 2009
doi: 10.1242/dev.033324

Development 136, 3099-3107 (2009)
Published by The Company of Biologists 2009
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Abi plays an opposing role to Abl in Drosophila axonogenesis and synaptogenesis

Tzu-Yang Lin1,*, Chiu-Hui Huang1,2,*, Hsiu-Hua Kao2, Gan-Guang Liou1, Shih-Rung Yeh2, Chih-Ming Cheng1, Mei-Hsin Chen1, Rong-Long Pan2 and Jyh-Lyh Juang1,{dagger}

1 Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.
2 Department of Life Science, National Tsing Hua University, Hsinchu 30043, Taiwan.

{dagger} Author for correspondence (juang{at}nhri.org.tw)

Accepted 2 July 2009

Abl tyrosine kinase (Abl) regulates axon guidance by modulating actin dynamics. Abelson interacting protein (Abi), originally identified as a kinase substrate of Abl, also plays a key role in actin dynamics, yet its role with respect to Abl in the developing nervous system remains unclear. Here we show that mutations in abi disrupt axonal patterning in the developing Drosophila central nervous system (CNS). However, reducing abi gene dosage by half substantially rescues Abl mutant phenotypes in pupal lethality, axonal guidance defects and locomotion deficits. Moreover, we show that mutations in Abl increase synaptic growth and spontaneous synaptic transmission frequency at the neuromuscular junction. Double heterozygosity for abi and enabled (ena) also suppresses the synaptic overgrowth phenotypes of Abl mutants, suggesting that Abi acts cooperatively with Ena to antagonize Abl function in synaptogenesis. Intriguingly, overexpressing Abi or Ena alone in cultured cells dramatically redistributed peripheral F-actin to the cytoplasm, with aggregates colocalizing with Abi and/or Ena, and resulted in a reduction in neurite extension. However, co-expressing Abl with Abi or Ena redistributed cytoplasmic F-actin back to the cell periphery and restored bipolar cell morphology. These data suggest that abi and Abl have an antagonistic interaction in Drosophila axonogenesis and synaptogenesis, which possibly occurs through the modulation of F-actin reorganization.

Key words: Abi, Abl, Drosophila, Genetic suppressor, Axon guidance, Synaptogenesis


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