Gene regulatory logic of dopamine neuron differentiation

摘要: Dopamine signalling regulates a variety of complex behaviours, and defects in dopamine neuron function or survival result severe human pathologies, such as Parkinson's disease. The common denominator all neurons is the expression pathway genes, which code for set phylogenetically conserved proteins involved synthesis transport. Gene regulatory mechanisms that direct activation genes thereby ultimately determine identity are poorly understood systems studied so far. Here we show simple cis-regulatory element, (DA) motif, controls dopaminergic cell types Caenorhabditis elegans. DA motif activated by ETS transcription factor AST-1. Loss ast-1 results failure distinct neuronal subtypes to terminally differentiate. Ectopic sufficient activate some cellular contexts. Vertebrate also contain motifs can be mouse Etv1 (also known ER81), specific class fails differentiate mice lacking Etv1. Moreover, ectopic induces fate marker primary cultures. Mouse functionally substitute C. Our studies reveal apparently logic terminal differentiation may provide new entry points into diagnosis therapy conditions defective.