Compositions and methods for real-time non-invasive monitoring of neuronal differentiation. Biosensor proteins comprising N-fusion and C-fusion proteins the express Adaptor Protein Complex 2 (AP2) and glutamate ionotropic receptor AMPA type subunit 2 (GRIA2), respectively, as well as split inteins and a reporter molecule enable the detection of hippocalcin via the translocation of a fluorescent protein into the nucleus of a cell.