Lola regulates Drosophila olfactory projection neuron identity and targeting specificity.
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.


CONCLUSIONS
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.
Spletter
Maria Lynn
ML
Howard Hughes Medical Institute, Department of Biological Sciences, Stanford University, Stanford, California 94305, USA. spletter@stanford.edu
Liu
Jian
J
Liu
Justin
J
Su
Helen
H
Giniger
Edward
E
Komiyama
Takaki
T
Quake
Stephen
S
Luo
Liqun
L
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D007814:Larva; D009833:Olfactory Pathways / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics
D029721:Drosophila Proteins; D014157:Transcription Factors; C121765:lola protein, Drosophila