The transcriptional code of adult motoneuron identity in Drosophila. Jonathan Enriquez^1*, Myungin Baek², Richard Mann¹. 1) Department of Biochemistry and Molecular Biophysic, Columbia University Medical Center , New York, NY; 2) NYU School of Medicine Neuroscience Program 522 First Avenue SML504 New York, NY 10016.

   Drosophila offers the possibility to study how sophisticated movements are coordinated by a small number of neurons. In each fly leg, around 50 motoneurons, generated from 11 neuroblast lineages, are used for walking and grooming. Two major lineages, called Lin A and Lin B, generate about 28 and 7 motoneurons respectively. Our goal is to understand how these neurons obtain their individual identities. Our hypothesis is that each adult leg motoneuron expresses a specific combinatorial code of transcription factors (TFs) that controls its identity. To identify candidate TFs, positively labeled Lin A and Lin B MARCM clones in L3 larvae were stained with antibodies directed against a large number of TFs. Because it contains fewer motoneurons, our initial focus was on Lin B, thus simplifying the analysis. The TFs identified are Empty spiracles (Ems), Kruppel (Kr), Zinc Finger Homeodomain Factors 1 and 2 (ZFH1/2), the Hox protein Proboscipedia (Pb), and Twin of Eyeless (Toy). Double and triple immunostains reveal a complex combinatorial code, consistent with our hypothesis. Subsequent genetic experiments reveal the consequences of genetically removing or ectopically expressing these TFs during motoneuron development. Both dendritic morphology and axon branching patterns were characterized. These observations support the idea that subsets of TFs regulate different aspects of motoneuron identity, depending on the context, in particular, which other TFs are present. In some cases, dendritic morphology was regulated independently from axon targeting, while in other cases they were coordinately regulated.