Neural Crest Origin of TSC Tumors
Technical Report,01 Jun 2018,31 May 2019
Columbia University in the City of New York New York
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Given the multi-organ manifestation of TS lesions, and the mesenchymal lineage of tumors recovered from TS patients, it has been postulated that TS is a neurocristopathy in which tumorigenesis is initiated by neural crest cells, but direct supporting experimental evidence has not been produced. We hypothesize that by tracking neurocristogenesis in a TSC2- mouse model, we will delineate the molecular mechanisms underlying temporal ontogenesis and progression of benign neoplasms characterizing TS and LAM. Furthermore, we hypothesize that HMGA2 misexpression defines tumorigenesis in TS and LAM caused by differentiating neural crest progenitor cells. This will subsequently lead to novel therapeutic approaches to the disease. Aim 1 To delineate the biochemical signaling that determines the temporal sequence of neural crest cell-induced initiation and progression of tumors using a TSC2- mouse model. Aim 2 To determine the role of HMGA2 in tumor pathogenicity driven by TSC2-haploinsufficient iPSC-derived neural crest precursors.
- Medicine and Medical Research