OTX2 Homeoprotein Functions in Adult Choroid Plexus

The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative functional roles for OTX2 in adult choroid plexus function, including cell signaling and adhesion, and show that OTX2 regulates the expression of factors that are secreted into the cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and affects splicing, leading to changes in the mRNA isoforms of proteins that are implicated in the oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell-autonomous target regions, such as the visual cortex and subventricular zone, we identify putative targets that are involved in cell adhesion, chromatin structure, and RNA processing. Thus, OTX2 retains important roles for regulating choroid plexus function and brain homeostasis throughout life.

Automated summary

This study explores the functional roles of OTX2 in adult choroid plexus, highlighting its importance in processes such as cell signaling, adhesion, and regulation of secreted factors. OTX2 is shown to impact immune responses, stress reactions in the choroid plexus, and influence the mRNA isoforms of proteins involved in oxidative stress response and DNA repair. Mass spectrometry analysis also reveals potential OTX2 protein partners in the choroid plexus and other target regions, involved in cell adhesion, chromatin structure, and RNA processing. Overall, OTX2 plays crucial roles in regulating choroid plexus function and brain homeostasis throughout life.