ABSTRACT: A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire
Project description:This SuperSeries is composed of the following subset Series: GSE34121: A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire (allele lola_ORE76) GSE34122: A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire (allele lola_ORC4) Refer to individual Series
Project description:A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire (allele lola_ORE76)
Project description:A genome-wide analysis reveals that the Drosophila transcription factor, Lola, promotes axon growth in part by suppressing expression of the actin nucleation factor, Spire (allele lola_ORC4)
Project description:Adult mammalian CNS neurons undergo a developmental switch in intrinsic axon growth ability associated with their failure to regenerate axons after injury. Krüppel-like transcription factors (KLF) regulate intrinsic axon growth ability, but signaling regulation upstream and downstream is poorly understood. Here we find that suppressing expression of KLF9, an axon growth suppressor normally upregulated 250-fold in retinal ganglion cell (RGC) development, promotes long-distance optic nerve regeneration in vivo. We identify a novel binding partner, MAPK10/JNK3, critical for KLF9’s axon growth suppressive activity. Additionally, by screening genes regulated by KLFs in RGCs, we identify dual-specificity phosphatase 14 (Dusp14) as key to limiting axon growth and regenerative ability downstream of KLF9, associated with its dephosphorylation of MAPKs critical to neurotrophic signaling of RGC axon elongation. These results now link intrinsic and extrinsic regulation of axon growth and suggest new therapeutic strategies to promote axon regeneration in the adult CNS.
Project description:Growth of the drosophila eye imaginal discs is controlled by the activation of Notch in the dorsal-ventral boundary. Overexpression in the eye disc of the Notch ligand Delta together with lola and pipsqueak from the GS(2)88A8 line induces tumoral growth. We used microarray to analyze the expression profile of tumoral discs.
Project description:longitudinals lacking (lola) is among the most complex genes in Drosophila melanogaster, encoding up to 20 different protein isoforms and acting as a key transcription factor in axonal pathfinding and neural reprograming. To better characterize Lola function we have generated specific mutations in each isoform using the CRISPR/Cas9 system. Our targeted screen allows us to revisit the previously demonstrated roles for few isoforms, to assign known functions to specific isoforms and to reveal a critical role for a specific variant in the octopaminergic pathway. Thus, our comprehensive study expands the repertoire of Lola functions, and demonstrates that the CRISPR/Cas9 approach is a valuable tool to systematically address the role of complex loci in vivo.
Project description:Longitudinals lacking (lola) is among the most complex genes in Drosophila melanogaster, encoding up to 20 different protein isoforms and acting as a key transcription factor in axonal pathfinding and neural reprograming. To better characterize Lola function we have generated specific mutations in each isoform using the CRISPR/Cas9 system. Our targeted screen allows us to revisit the previously demonstrated roles for few isoforms, to assign known functions to specific isoforms and to reveal a critical role for a specific variant in the octopaminergic pathway. Thus, our comprehensive study expands the repertoire of Lola functions, and demonstrates that the CRISPR/Cas9 approach is a valuable tool to systematically address the role of complex loci in vivo.
Project description:Longitudinals lacking (lola) is among the most complex genes in Drosophila melanogaster, encoding up to 20 different protein isoforms and acting as a key transcription factor in axonal pathfinding and neural reprograming. To better characterize Lola function we have generated specific mutations in each isoform using the CRISPR/Cas9 system. Our targeted screen allows us to revisit the previously demonstrated roles for few isoforms, to assign known functions to specific isoforms and to reveal a critical role for a specific variant in the octopaminergic pathway. Thus, our comprehensive study expands the repertoire of Lola functions, and demonstrates that the CRISPR/Cas9 approach is a valuable tool to systematically address the role of complex loci in vivo.
