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The Neuroscientist Comments

What are the molecular control mechanisms that push some neuronal progenitors to develop into sensory neurons, others into Renshaw cells, and still others into Purkinje cells? A large body of work has identified molecular mechanisms that regulate early neuronal specification, including transcription factors and fate-determination genes that control early aspects of neurogenesis in a number of parts of the CNS. Less, however, is known about molecular mechanisms that control later aspects of differentiation of the distinct subtypes of neurons. This problem is especially challenging within the cortex, where there are many different classes of projection neurons, which send their axons to different cortical, subcortical, or subcerebral targets, in many cases in a specific ipsilateral or contralateral manner. To begin to address this problem, Arlotta and others (2005) have focused on corticospinal motor neurons. After purifying these neurons at distinct stages of development in vivo, they compared gene expression in these cells with two other types of cortical projection neurons, callosal projection neurons and corticotectal projection neurons. Using microarray gene chips, they found a number of genes that are potentially instructive for corticospinal motor neuron development, together with other genes that are excluded from the corticospinal motor neurons and appear to be restricted to other neuronal populations, even within the same cortical layer. One of the newly characterized genes, Ctip (also known as Bcl 11b), appears, on the basis of experiments in null mutant mice, to play a pivotal role in the development of corticospinal motor neuron axonal projections to the spinal cord. This study identifies some of the control mechanisms that regulate the development of specific neuronal subtypes in the cortex. Although multiple lock-andkey controls are likely to be involved in the regulation of neuronal differentiation, at least one of them appears to have now been identified.