During vertebrate development, retinoic acid (RA) signalling helps to shape the neural tube and consequently the central nervous system. Although several retinaldehyde dehydrogenases can synthesize RA from vitamin A, the most important of these during development is Raldh2. Now, José Xavier-Neto and colleagues identify a conserved intronic enhancer that drives raldh2 expression in the roof plate and dorsal-most (dl1) interneurons of frog, mouse and chicken embryos (see p. ). This enhancer is activated dorsally through Tcf- and Cdx-homeodomain binding sites, they report, and repressed ventrally through Tgif-homeobox and Lim-homeodomain binding sites. Other experiments reveal a novel transient expression domain for raldh2 in dl1 interneurons, which suggests that RA signalling regulates the development of spinocerebellar and intraspinal proprioceptive (movement perception) circuits. Finally, the researchers report that raldh2 is also expressed in dorsal spinal cord interneurons in lamprey embryos. Because the lamprey is an agnathan, an ancient order of vertebrates, this observation reveals ancestral roles for RA signalling during the development of intraspinal proprioception.
