Neuroblastoma (NB) is a childhood cancer which thought to derive because of improper differentiation of trunk neural crest cells (tNCCs) which form the sympatho-adrenergic lineage. Crest cells are versatile in nature as they can give rise to many different cell types but are less studied because of lack of proper model system. MYCN is frequently amplified in high risk NBs but it is not properly understood how MYCN affects the gene expression in tNCCs. The current proposal aim to unravel mechanistically how MYCN plays a critical role in the early transformation of the tNCCs using transcriptomics and epigenomic based approaches. The survival outcome of high risk NB patients is still 50% which warrant for developing novel drugs for the treatment. We aim to develop specific inhibitor for a deubiquitinase USP36 which regulates the stability of the MYCN protein in NB cells. Recent high-throughput technologies have revealed wide spread transcription across human genome which produces thousands of long noncoding RNA (lncRNAs). Though lncRNA function has been studied in different cellular model system their role in tNCC biology is still unexplored. We described a unique functional screen approach to identify tNCC specific lncRNAs with importance to NB. The current proposal along with the strong foundation of preliminary data has the potential to take forward the observation of the basic biology to the development of novel therapeutic intervention for NBs.