Lola regulates Drosophila olfactory projection neuron identity and targeting specificity

Maria Lynn Spletter¹ , Jian Liu²^,3 , Justin Liu¹ , Helen Su¹^,4 , Edward Giniger⁵ , Takaki Komiyama¹^,4 , Stephen Quake² and Liqun Luo¹

¹Howard Hughes Medical Institute, Department of Biological Sciences, Stanford University, Stanford, California 94305, USA

²Howard Hughes Medical Institute, Department of Bioengineering, Stanford University, Stanford, California 94305, USA

³Department of Biomedical Engineering, Emory University, Atlanta, Georgia 30322, USA

⁴Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA

⁵National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA

author email corresponding author email

Neural Development 2007, 2:14doi:10.1186/1749-8104-2-14


Published:	16 July 2007

Abstract

Background

Precise connections of neural circuits can be specified by genetic programming. In the Drosophila olfactory system, projection neurons (PNs) send dendrites to single glomeruli in the antenna lobe (AL) based upon lineage and birth order and send axons with stereotyped terminations to higher olfactory centers. These decisions are likely specified by a PN-intrinsic transcriptional code that regulates the expression of cell-surface molecules to instruct wiring specificity.

Results

We find that the loss of longitudinals lacking (lola), which encodes a BTB-Zn-finger transcription factor with 20 predicted splice isoforms, results in wiring defects in both axons and dendrites of all lineages of PNs. RNA in situ hybridization and quantitative RT-PCR suggest that most if not all lola isoforms are expressed in all PNs, but different isoforms are expressed at widely varying levels. Overexpression of individual lola isoforms fails to rescue the lola null phenotypes and causes additional phenotypes. Loss of lola also results in ectopic expression of Gal4 drivers in multiple cell types and in the loss of transcription factor gene lim1 expression in ventral PNs.

Conclusion

Our results indicate that lola is required for wiring of axons and dendrites of most PN classes, and suggest a need for its molecular diversity. Expression pattern changes of Gal4 drivers in lola^-/-clones imply that lola normally represses the expression of these regulatory elements in a subset of the cells surrounding the AL. We propose that Lola functions as a general transcription factor that regulates the expression of multiple genes ultimately controlling PN identity and wiring specificity.