title: Huntingtin Is Required for Neural But Not Cardiac/Pancreatic Progenitor Differentiation of Mouse Embryonic Stem CellsIn vitro.
abstract: Mutation in the huntingtin (HTT) gene causes Huntington's disease (HD). It is an autosomal dominant trinucleotide-repeat expansion disease in which CAG repeat sequence expands to >35. This results in the production of mutant HTT protein with an increased stretch of glutamines near the N-terminus. The wild typeHTTgene encodes a 350 kD protein whose function remains elusive. Mutant HTT protein has been implicated in transcription, axonal transport, cytoskeletal structure/function, signal transduction, and autophagy. HD is characterized by the appearance of nuclear inclusions and degeneration of the striatum. Although HTT protein is expressed early in embryos, most patients develop symptoms in mid-life. It is also unclear why the ubiquitously expressed mutant HTT specifically causes striatal atrophy. Wild type Htt is essential for development asHttknockout mice die at day E7.5. Increasing evidence suggests mutant Htt may alter neurogenesis and development of striatal neurons resulting in neuronal loss. Using a mouse embryonic stem cell model, we examined the role of Htt in neural differentiation. We found cells lacking Htt inefficient in generating neural stem cells. In contrast differentiation into progenitors of mesoderm and endoderm lineages was not affected. The data suggests Htt is essential for neural but not cardiac/pancreatic progenitor differentiation of embryonic stem cellsin vitro.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York NY, USA.
authors.forename: Man Shan
authors.initials: MS
authors.lastname: Yu
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York NY, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tanese
keywords: Huntington’s disease; embryoid bodies; embryonic stem cells; huntingtin gene; neural differentiation; neural stem cells