Tuberin levels during cellular differentiation in brain development

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex (TSC), and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, permits the formation of tumors that can lead to developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that total Tuberin levels are tightly regulated through developmental stages in the embryonic brain. At a cell biology level, we show that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. This functional data supports the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

Automated summary

Tuberin, a member of the Tuberous Sclerosis Complex (TSC) protein complex, acts as a nutrient sensor and regulates protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, can lead to tumor formation and developmental defects in multiple organ systems, including the central nervous system. Our study investigates the regulation of Tuberin levels during embryonic brain development in vivo and in immortalized cell lines in vitro. The results show that Tuberin levels are tightly regulated during different developmental stages and play a role in stemness and functional differentiation in the central nervous system.