Genetic pathways in the developmental differentiation of midbrain dopaminergic neurons
DU Fang,LI Rui,LE Wei-dong ( Health Science Center of Shanghai Institutes for Biological Sciences,CAS;Institute of Biomedical Sciences,Rui Jin Hospital,Shanghai Second Medical University,Shanghai 200025,China )
Midbrain dopaminergic system,which is associated with many important neurological and mental disorders,is intensively studied. The developmental course of dopaminergic neurons is a highly controlled process involving multiple transcription factors and growth factors acting together in genetic pathways. In the early stage of embryo,the homeodomain proteins controlling midbrain development regulate the proliferations and migration of dopaminergic progenitor cells. Following the expression of the specific transcription factors in the birth of midbrain dopaminergic neurons,Nurr1 and Ptx3,dopaminergic phenotype emerges and dopaminergic synthesis is activated. At last,the maturation of dopaminergic neurons requires specific interactions with the developing target striatal cells,and multiple environmental cues involved at the different times in the development of dopaminergic neurons.