| Summary: | During development, mesodiencephalic dopaminergic (mdDA) neurons form into different molecular subsets. Knowledge of which factors contribute to the specification of these subsets is currently insufficient. In this study, we examined the role of <i>Tcf4</i>, a member of the E-box protein family, in mdDA neuronal development and subset specification. We show that <i>Tcf4</i> is expressed throughout development, but is no longer detected in adult midbrain. Deletion of <i>Tcf4</i> results in an initial increase in TH-expressing neurons at E11.5, but this normalizes at later embryonic stages. However, the caudal subset marker <i>Nxph3</i> and rostral subset marker <i>Ahd2</i> are affected at E14.5, indicating that <i>Tcf4</i> is involved in correct differentiation of mdDA neuronal subsets. At P0, expression of these markers partially recovers, whereas expression of <i>Th</i> transcript and TH protein appears to be affected in lateral parts of the mdDA neuronal population. The initial increase in TH-expressing cells and delay in subset specification could be due to the increase in expression of the bHLH factor <i>Ascl1</i>, known for its role in mdDA neuronal differentiation, upon loss of <i>Tcf4</i>. Taken together, our data identified a minor role for <i>Tcf4</i> in mdDA neuronal development and subset specification.
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