Figure 1.

The multi-facet functions of Auts2. Auts2 participates in transcriptional and epigenetic regulations, neuronal differentiation, neuronal migration, neuritegenesis as well as synapse formation. In the aspect of transcriptional regulation, the expression of Auts2 is controlled by transcriptional factors (TFs) such as Mecp2 and Tbr1. Moreover, Auts2 is a transcriptional regulator itself. It can control the expression of other TFs (e.g., TCF3, Pitx3, and FOXO3), cell adhesion molecules (e.g., NRXNs and CNTNs), axonal guidance molecules (e.g., SEMAs) and proteins involved in synaptic functions (e.g., Reln, Mdga1, and Camk2b). The precise coordinate of transcription by Auts2 is critical for neuronal differentiation and synapse formation. The deletion of Auts2 gene can lead to behavior impairment in social interaction, cognition, and ultrasonic vocalization, which captures the features observed in patients with neurodevelopmental disorders such as ASD. Auts2 also plays important roles in epigenetic regulations. After binding PCGF3/PCGF5, RING1 and P300, the Auts2-containing complex can bind to the promotor regions of various genes and modify histones. Through epigenetic regulation, Auts2 can mediate the effect of environmental factors, e.g., chemicals and maternal health factors on the nervous system. Cytoplasmic Auts2 regulates the neuronal migration and neuritegenesis through inducing lamellipodia and suppressing filopodia. The function of Auts2 in circuits remains to be further explored.