Olig genes and the genetic logic of CNS neural cell fate determination

Abstract

The three fundamental cell types of the vertebrate CNS are neurons, astrocytes and oligodendrocytes. The molecular mechanisms that generate this basic triad remain poorly understood. Transcription factors in the basic helix-loop-helix (bHLH) family have been shown to play an important role in the fundamental choice between neuronal and glial fates, while homeodomain transcription factors have been shown to determine different aspects of neuronal subtype identity. However, the transcriptional control of the choice between oligodendrocyte and astrocyte fates has not been elucidated. Here we describe a novel family of bHLH factors, called Olig1 and Olig2, that is specifically expressed in oligodendrocyte precursors throughout the CNS. Genetic studies indicate that Olig1/2 promote motoneuron and suppress interneuron fates during the neurogenic phase of spinal cord development, while at later stages they promote the oligodendrocyte and suppress the astrocyte fates. In this way, these factors couple neuronal subtype specification to glial subtype specification. In conjunction with the proneural subclass of bHLH factors, such as the Neurogenins, Olig genes can define a simple combinatorial code that determines whether CNS progenitors will adopt neuronal, oligodendroglial or astroglial fates. This genetic logic offers a framework for understanding the basic mechanisms that generate the three fundamental cell types of the vertebrate CNS.

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