Insights into the organization of dorsal spinal cord pathways from an evolutionarily conserved raldh2 intronic enhancer

Abstract

SUMMARYComparative studies of the tetrapod raldh2 (aldh1a2) gene, which encodes a retinoic acid (RA) synthesis enzyme, have led to the identification of a dorsal spinal cord enhancer. Enhancer activity is directed dorsally to the roof plate and dorsal-most (dI1) interneurons through predicted Tcf-and Cdx-homeodomain binding sites and is repressed ventrally via predicted Tgif homeobox and ventral Lim-homeodomain binding sites. Raldh2 and Math1/Cath1 expression in mouse and chicken highlights a novel, transient, endogenous Raldh2 expression domain in dI1 interneurons, which give rise to ascending circuits and intraspinal commissural interneurons, suggesting roles for RA in the ontogeny of spinocerebellar and intraspinal proprioceptive circuits. Consistent with expression of raldh2 in the dorsal interneurons of tetrapods, we also found that raldh2 is expressed in dorsal interneurons throughout the agnathan spinal cord, suggesting ancestral roles for RA signaling in the ontogenesis of intraspinal proprioception.

Finding a Needle in a Genomic Haystack

“…A similar picture is emerging for TCFs and AP-1, where Wnt and mitogenic signals converge (Bottomly et al, 2010;Domenzain-Reyna et al, 2009;Nateri, Spencer-Dene, and Behrens, 2005). Other examples are Cdx proteins and TCFs, where Cdx1 associates with LEF1 (Beland et al, 2004), TCF4 binding to chromatin is reduced a Cdx2 mutant cells (Verzi et al, 2010) and functional TCF and Cdx binding sites are found in close proximity in a chick WRE (Castillo et al, 2010).…”

Humans Walking on all Four Extremities with Mental Retardation and Dysarthric or no Speech: A Dynamical Systems Perspective

“…Accordingly, it was reported an evolutionarily conserved daldh2 intronic enhancer in the frog, mouse, and chicken, being also involved in the formation of the neural tube throughout vertebrate species [7]. This evolutionary conservation of the enzyme playing a role in shaping the neural tube is essentially related to the evolutionary conservation of the neural networks for the diagonalsequence QL.…”

The dorsal neural tube: A dynamic setting for cell fate decisions

“…Furthermore, Raldh2, a RA synthetic enzyme is the first Raldh to appear in mouse and chick embryos, and overlaps with sites of RA signaling (Zhao et al, 1996;Niederreither et al, 1997;Moss et al, 1998;Ulven et al, 2000;Xavier-Neto et al, 2000;Blentic et al, 2003;Lin et al, 2003). Recently, a conserved intronic enhancer that drives raldh2 expression in the RP and dorsal interneurons of frog, mouse, and chicken was identified (Castillo et al, 2010). Moreover, both CRAPB and RA receptor a (RAR a) were also detected in emigrating and migrating NC cells and in NC-derived DRG, SG and enteric ganglia (Ruberte et al, 1991).…”