The central nervous system (CNS) contains roughly 100 billion neurons that are selectively connected via 100 trillion synapses creating highly specific circuits. Any developmental insults to these processes can result in the onset of neurodevelopmental disorders or brain neoplasm. Our laboratory is interested in understanding the mechanisms underlying the fundamental development and maintenance of the mammalian brain. Neuronal development and maturation rely on extrinsic and intrinsic cues to optimally guide neuronal identity and maintenance. The extrinsic signals can arise from within the same tissue, from blood or cerebrospinal fluids (CFS). CSF is mainly produced by the choroid plexus (CP), a specialized epithelial layer located in each ventricle in the brain. Our working hypothesis is that the CP secretes instructive signals into the CSF that may exert an endocrine-like effect on target cells in the brain, instructing developing neurons in an age-dependent manner. We are employing a multi-tiered approach that draws on molecular neuroscience, developmental neurobiology, proteomics transcriptomics and imaging to identify unbiased instructive signals fundamental to brain maturation. The identification of these cues could have tremendous potential for unlocking brain plasticity and for developing new therapies to prevent neoplasm malignancy.