Nuclear Factor-Y Controls Neurite Extension by Balancing BMP Signaling

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. Significance statement Correct nervous system development requires precise neurite guidance and termination. Over the last four decades, the guidance molecules controlling these events have been extensively studied, whereas transcriptional regulation of these molecules remains poorly understood. We reveal an important role for the Nuclear Factor-Y transcription factor (NF-Y) in controlling distinct neurodevelopmental events. By specifically focusing on neurite extension, we show that NF-Y acts in parallel with multiple established neuronal architects to promote correct neurite development. Intriguingly, inducing the Bone Morphogenetic Protein (BMP) pathway corrects aberrant neurite extension caused by NF-Y loss. These findings provide insight into how nervous system architecture is controlled by a conserved transcriptional regulator and the crucial connection between NF-Y and the BMP pathway during neurite extension.