Retinoic acid and the control of dorsoventral patterning in the avian spinal cord

Abstract

The development of neural subtypes in the dorsoventral (DV) axis of the vertebrate central nervous system (CNS) involves the integration of signalling pathways coupled with the combinatorial expression of homeodomain transcription factors. Previous studies have implicated a role for retinoic acid in the specification of a subtype of motor neurons (MN) and in the patterning of a group of interneurons within the ventral spinal cord. In this study, we use the vitamin A-deficient (VAD) quail model to further investigate the role of retinoids in the patterning of the neural tube. Using genetic markers specific to neuronal cell populations, we demonstrate that in the absence of retinoic acid, there is a disruption to the molecular mechanisms associated with the dorsoventral patterning of the spinal cord. In particular, we observe an uneven dorsal expansion of ventral-specific genes, accompanied by a reduction in the domain of roof plate and dorsal patterning genes, both of which are rescued upon addition of retinoids during development. In addition, there is a loss of V1 interneuron-specific gene expression and a decrease in the ventricular zone expression of motor neuron patterning genes. Interestingly, these effects are localised to the rostral half of the spinal cord, indicating that RA is integrated in both anteroposterior (AP) and dorsoventral patterning processes. Using differential display techniques, we have isolated 27 retinoic acid-regulated genes within the spinal cord that together reveal several interesting potential biological functions for retinoids within the avian neural tube. In summary, we propose that retinoids have an essential role in the patterning of the dorsoventral axis of the spinal cord, and are also required for the correct integration of anteroposterior patterning signals with dorsoventral determinants in the rostral spinal cord.