Nuclear Factor-Y Controls Neurite Extension by Balancing BMP Signaling

Abstract

Neuronal circuit formation is controlled by secreted guidance molecules and their receptors. However, the transcriptional mechanisms underlying neuronal circuit formation are not fully understood. In an unbiased genetic screen, we identified the Nuclear Factor-Y transcription factor (NF-Y) as a key regulator of neuron fate and axon guidance. NF-Y is a highly conserved and ubiquitous complex, composed of three subunits: NF-YA, NF-YB, and NF-YC. The NF-YA subunit directly binds to regulatory regions of target genes to control their expression. Here, we show that NFYA-1 controls neurite development of multiple neuronal subtypes in Caenorhabditis elegans . Using the serotonergic neurosecretory-motor neurons (NSM) neurons as a model, we discovered that NFYA-1 acts cell-autonomously to limit NSM dorsal neurite length. Further, NSM neurite overextension caused by NFYA-1 loss is suppressed by overactivating DBL-1/BMP (Bone Morphogenetic Protein) signaling. A previous study found that in Drosophila melanogaster , NF-YC regulates axon targeting of photoreceptor neurons. Thus, NF-Y likely plays a broad role in shaping neuronal circuitry across species, albeit through distinct mechanisms.