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Investigating neurogenesis with biosensors directed at key transcription factors
Author(s) -
Stoddard Matthew R,
Bonham Andrew J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.547.7
Subject(s) - neurogenesis , transcription factor , biology , gene , tbx1 , progenitor cell , neural stem cell , microbiology and biotechnology , cell fate determination , pax6 , genetics , gene expression , stem cell , promoter
Neurogenesis, the process by which neural stem and progenitor cells turn into functional neurons, is heavily regulated. Much of this regulation comes from the interplay of transcription factor proteins that direct the expression of key genes. Two of these transcription factors are the proteins Ascl1 and Lmo4 which regulate genes involved in neuronal commitment and the generation of autonomic neurons among other important genes in development of nervous cells. Ascl1 and Lmo4 mutants are known to be involved in human diseases including neuroblastomas and small cell lung cancers. Deletion of either gene has resulted in death when tested in mouse models. Many details of the roles Ascl1 and Lmo4 play in neurogenesis, human disease, and how they interact with one another are not fully understood. To address these outstanding questions, we are generating sensitive, DNA‐based biosensors for the quantitative detection of the DNA‐binding activity of these significant proteins. These sensors will be used with recombinantly expressed and purified constructs of human Ascl1 and Lmo4, with the goal of determining the effect of protein‐protein interaction on their regulatory activity.