Yishu - Journal of Contemporary Chinese Art

2 Dysfunction of the serotonergic system gives rise to a

Friday, July 26th, 2013

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canada goose clearance Vs. Manchester. City. Live. 2014 15. Seasons. Top of pageIntroductionDespite their small numbers (26 in the mouse brain1), serotonergic neurons exert diverse and widespread impact on emotion, feeding, aggression, compulsion, sleep and so on.2 Dysfunction of the serotonergic system gives rise to a variety of neurological disorders and mental illnesses, including depression, anxiety, obsessive compulsive disorder, autism and eating disorder.2 Increasing evidence suggest that individual variations in genes controlling the development and function of serotonergic neurons may lead to a variety of serotonin related brain disorders.3 Thus, it would be very useful to generate patient specific serotonergic neurons for mechanistic studies of serotonergic dysfunctions and drug discovery research on many serotonin related brain diseases. Recent research on transdifferentiation has shown that fibroblasts can be directly converted by different sets of transcription factors to different types of cells.4 Ascl1 is a key transcription factor for neurogenesis and early neural differentiation.5 It serves as a pioneer factor in the transdifferentiation of fibroblasts to induced neurons.6 In Ascl1 knockout mice, there is a profound loss of serotonin, as transcription factors that specify serotonergic neurons such as Pet1 and Lmx1b are not expressed.7 FoxA2 establishes the progenitor domains for the precursors of serotonergic neurons in the ventral hindbrain and activates transcription factors required for the terminal differentiation of serotonergic neurons, such as Pet1 and Lmx1b.8 Loss of FoxA2 at the precursor stage ablates 50 of serotonergic neurons in the hindbrain.8 Lmx1b is a critical transcription factor in the terminal differentiation of serotonergic neurons. In Lmx1b deficient mice, precursors of serotonergic neurons are generated in normal numbers, but they fail to express the battery of genes (Tph2, Sert, Vmat2 and so on) that define a serotonergic neuron.9, 10 Deletion of Lmx1b specifically in serotonergic neurons results in the loss of these early precursors, confirming the role of Lmx1b in the terminal differentiation of serotonergic neurons.11 Pet1 (FEV in human) expression is restricted to serotonergic neurons.12, 13 Pet1 deficient precursor cells fail to turn on the expression of serotonergic marker genes, such as Tph2, Aadc, Vmat2, Sert and Maob, resulting in a loss of 70 serotonergic neurons.14 canada goose clearance.

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