developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system发育转录网络需要维持神经元亚型的身份在成熟的神经系统.pdfVIP

Developmental Transcriptional Networks Are Required to Maintain Neuronal Subtype Identity in the Mature Nervous System Kevin T. Eade, Hailey A. Fancher, Marc S. Ridyard, Douglas W. Allan* Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada Abstract During neurogenesis, transcription factors combinatorially specify neuronal fates and then differentiate subtype identities by inducing subtype-specific gene expression profiles. But how is neuronal subtype identity maintained in mature neurons? Modeling this question in two Drosophila neuronal subtypes (Tv1 and Tv4), we test whether the subtype transcription factor networks that direct differentiation during development are required persistently for long-term maintenance of subtype identity. By conditional transcription factor knockdown in adult Tv neurons after normal development, we find that most transcription factors within the Tv1/Tv4 subtype transcription networks are indeed required to maintain Tv1/Tv4 subtype- specific gene expression in adults. Thus, gene expression profiles are not simply ‘‘locked-in,’’ but must be actively maintained by persistent developmental transcription factor networks. We also examined the cross-regulatory relationships between all transcription factors that persisted in adult Tv1/Tv4 neurons. We show that certain critical cross-regulatory relationships that had existed between these transcription factors during development were no longer present in the mature adult neuron. This points to key differences between developmental and maintenance transcriptional regulatory networks in individual neurons. Together, our results provide novel insight showing that the maintenance of subtype identity is an active process underpinned by persistently active, combinatorially-acting, deve