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.

Retinoic acid is both necessary for and inhibits myogenic commitment and differentiation in the chick limb

“…Treatment with the RA inhibitor citral resulted in down-regulation of expression of myogenic genes in both progenitor cells (Pax3 and Meox2, Meox2 down-regulation was greater than that of Pax3) and myoblasts committed to differentiation (Myf5 and MyoD, MyoD down-regulation was greater than that of Myf5). These results are consistent with the down-regulation in expression of neural Pax3 and the myogenic differentiation gene Myogenin in somites in the absence of RA, as reported in the vitamin A deficient quail (Wilson et al, 2004;Maden et al, 2000). Additionally, in vivo studies in zebrafish embryos demonstrated that RA signalling is required for onset of myogenic differentiation in somites (Hamade et al, 2006).…”

Retinoic acid is required for specification of the ventral eye field and for Rathke's pouch in the avian embryo

“…We and others have used this model system extensively to characterise the regions of the early embryo which develop abnormally in the absence of RA. These include the cardiovascular system , the somites (Maden et al 2000), the hindbrain (Maden et al 1996;Gale et al 1999;), the pharyngeal arches (Quinlan et al 2002) and spinal cord (Wilson et al 2004). We report the observation that the VAD quail fails to develop the ventral part of the retina including the choroid fissure and that this is likely to be caused by an earlier defect at the ventral midline of the developing central nervous system involving a narrowing of the Shh domain.…”

Generation of V2a Interneurons from Mouse Embryonic Stem Cells

“…RA released from the somites during neural tube development is an inducer of neural differentiation and influences the rostral-caudal identity of cells in vitro with lower concentrations inducing more rostral cell types [15,43]. Studies have also shown that RA activates the expression of bHLH transcription factors to control the differentiation of neuronal cell types, such as V2a interneurons [44].…”