Retinoids are involved in a plethora of events during vertebrate neural development, including various aspects of neural tube patterning and neurogenesis. Three papers in Neuron provide some interesting new additions for their functional repertoire.

Diez del Corral et al. investigated caudal extension of the spinal cord in chick embryos. Previous work has shown that spinal cord progenitor cells reside in a 'stem zone', and fibroblast growth factor (FGF) signalling keeps them in an undifferentiated state. Unidentified signals from the somites that counteract FGF signalling cause these cells to differentiate and contribute to the growing spinal cord. Diez del Corral et al. now show that retinoic acid (RA) is one such signal. They present a model in which the balance between stem zone maintenance and neuronal differentiation is maintained by opposing gradients of Fgf8 and RA. As the Fgf8-expressing primitive streak regresses caudally, RA synthesis is activated, and this causes further repression of FGF signalling.

Novitch et al. show that retinoid signalling is also required for the specification of motor neurons in the ventral neural tube. Most of the signals that control ventral neuronal cell fate seem to be transcriptional repressors, but the authors found that activated retinoid receptors act as transcriptional activators for the homeodomain genes that specify the motor neuron progenitor domain. In addition, RA signalling promotes the adoption of a neuronal fate by activating the proneural gene Olig2.

Last, as Sockanathan et al. demonstrate, retinoids are also involved in postmitotic events in motor neurons. Although all motor neurons derive from a single domain along the dorsoventral axis of the neural tube, postmitotic motor neurons diversify along the anteroposterior axis to generate a series of motor columns. The authors show that RA is required for the specification of lateral motor column (LMC) neurons at the brachial level of the spinal cord, and that it also has a more general role in specifying LMC identity. Retinoid signalling also seems to control the acquisition of other motor neuron characteristics, including their positioning within the spinal cord and their axonal projection patterns.

These findings reveal crucial roles for retinoids in the extension of the spinal cord and the specification and differentiation of motor neurons, thereby sealing their reputation as key regulators of neural development.