NOS1APc associates with Hippo Signaling components and contributes to spinal cord development

Abstract

The nitric oxide synthase 1 adaptor protein (NOS1AP) is an adaptor protein implicated in a number of human conditions including schizophrenia, anxiety and cardiac QT syndrome. Previous studies have shown that NOS1AP and some of its isoforms associate with the tumor suppressor protein scribble. Since scribble has been linked to the Hippo pathway, I set out to determine if NOS1AP associates with the Hippo pathway and whether it controls aspects of neuronal development. Here I show that NOS1AP and NOS1APc interact with the transcriptional co-activator yes-associated protein (YAP), a component of the Hippo cascade. Further both NOS1APa and NOS1APc show partial co-distribute with YAP in HEK293Tcells, with NOS1APc having better co-distribution. In situ hybridization and immunocytochemistry studies reveal that NOS1APc is expressed in the developing spinal cord. NOS1APc is expressed in the floor plate and roof plate and shows a similar profile to radial glial cells. In ovo electroporation of cDNA constructs encoding NOS1APc in the developing spinal cord induced ectopic SOX2+ rosettes in the marginal zone similar to that seen with Yap overexpression, implicating NOS1APc in cellular proliferation. Taken together, these data suggests NOS1APc plays a role in the developing spinal cord, acting through the Hippo signaling pathway to affect neural progenitor cellular differentiation.