Maintenance of postmitotic neuronal cell identity

Abstract

The identity of specific cell types in the nervous system is defined by the expression of neuron type-specific gene batteries. How the expression of such batteries is initiated during nervous system development has been under intensive study over the past few decades. However, comparatively little is known about how gene batteries that define the terminally differentiated state of a neuron type are maintained throughout the life of an animal. Here we provide an overview of studies in invertebrate and vertebrate model systems that have carved out the general and not commonly appreciated principle that neuronal identity is maintained in postmitotic neurons by the sustained, and often autoregulated, expression of the same transcription factors that initiate terminal differentiation in a developing organism. Disruption of postmitotic maintenance mechanisms may result in neuropsychiatric and neurodegenerative conditions.

Figure 1. Initiation and maintenance of neuronal identity

Regulatory factors expressed transiently in the lineage that gives rise to a specific neuron type induce the expression of terminal selector–type transcription factors. These factors then initiate terminal differentiation by directly activating the expression of terminal effector genes, such as genes coding for neurotransmitter synthesizing enzymes, transporter and receptors, ion channel, synaptic adhesion molecules and so on. The activated state of these effector genes is maintained via the terminal selectors that initiated their expression. Such maintenance is made possible through the often observed autoregulation of terminal selectors. Other factors that played no role in initiating effector genes may assist terminal selectors in maintaining the differentiated state. In at least one case examined, these maintenance factors are controlled by terminal selectors as well (see text).