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Today I would like to highlight "fruitless Splicing Specifies Male #Courtship #Behavior in #Drosophila" https://www.cell.com/cell/fulltext/S0092-8674(05)00407-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867405004071%3Fshowall%3Dtrue @CellCellPress from Demir and @BarryJDickson - a paper which stands at the beginning of the renaissance of neurogenetics in #Drosophila #apaperaday
This paper is a very special one for me as I was lucky to see it being made @IMPvienna and it was one of the main reasons I started working on #behavior #neuroscience #apaperaday #covid19 #ScienceTwitter #ScienceFromHome #Read #AcademicTwitter
On Monday we discussed one of the iconic early papers in #Drosophila #neurogenetics https://twitter.com/RibeiroCarlitos/status/1247206520720371712 - But how strongly do genes really influence complex behavioral repertoires? Fly mutants for the fruitless gene made an important contribution to that discussion.
What some readers might not realize is that flies, like most animals, and especially insects, have very complex courtship rituals. And the behavior of males and females are very different. #sex #neuroscience
Early work starting with Sturtevant in 1910, continued by the Benzer, Hall, Yamamoto and Baker labs had helped to establish #Drosophila courtship #behavior as a fertile ground to study how the brain encodes behavior.
And fruitless seemed to be a key gene for deciding if a fly behaved like a male or a female. But are there genetic switches determining if a brain displays complex female or male behaviors? This excellent review by Baker, Taylor and Hall suggested yes: https://www.cell.com/cell/fulltext/S0092-8674(01)00293-8
fruitless (fru) is a super complex gene with many splice variants, but the P1 transcript seemed to be key for the courtship function of fru. fru exists in a male splice variant which encodes a protein expressed in neurons and a female splice variant without a protein.
The genius of @BarryJDickson was to realize that the newly developed genome engineering technologies allowed to test if it was this difference in splicing which encoded the "genetic switch" for courtship.
Ebru Demir, a graduate student in the lab set out to engineer flies in which the splicing of fru was altered so that males would either only express the female (fruF) form or the females would only express the male form (fruM). This was a heroic effort! And it worked!
But what happens to the behavior of these animals? Would courtship be abolished? Would females be confused, having a female body and some male neurons? Would they display a mix of female and male behavior?
In this movie you can appreciate the intricate courtship behavior of #Drosophila and pay special attention to the song part in which the male extends its wings to the "sing" to the female. #sexy #courtship #neuroscience
So what about our engineered fruM females whose brain expresses the male fruitless form? This movie shows a fruM female interacting with a control virgin female: Indeed the engineered female thinks it is a male and courts the other female vigorously!
But even more spectacular was the phenotype of fruF males. Watch this video to see what happens when you put multiple of these animals together: They form a courtship chain - a behavior which is mainly observed in fru mutants!
Importantly fruM males behaved like males and fruF females like females! This paper was a spectacular proof that a gene could change ("encode") complex behavioral patterns and that modern genetic techniques could be used to dissect this!
Demir and Dickson with Stockinger et al. in which the @BarryJDickson lab used genome engineering to manipulate the neurons in which fru is expressed https://www.cell.com/cell/fulltext/S0092-8674(05)00406-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS009286740500406X%3Fshowall%3Dtrue were more than papers - they a vision to use neurogenetics to tackle the #circuit basis of behavior
Many more classic papers followed from these. Watching them being made was tremendously exciting and inspiring. I still remember @BarryJDickson showing me the first fru data before I joined his lab in a bar late at night after a session of the European Drosophila meeting.
And these papers convinced me that maybe the genetic, molecular and behavioral tools were there to start dissecting the precise molecular and neuronal circuits basis of how the #brain works. And I switched from working on axon guidance to studying behavior.
