Insights into the organization of dorsal spinal cord pathways from an evolutionarily conserved raldh2 intronic enhancer.
Comparative 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.
Castillo
Hozana A
HA
Laboratorio de Genética e Cardiologia Molecular, InCor-FMUSP, 05403-000, São Paulo, Brazil.
Cravo
Roberta M
RM
Azambuja
Ana P
AP
Simões-Costa
Marcos S
MS
Sura-Trueba
Sylvia
S
Gonzalez
Jose
J
Slonimsky
Esfir
E
Almeida
Karla
K
Abreu
José G
JG
de Almeida
Marcio A Afonso
MA
Sobreira
Tiago P
TP
de Oliveira
Saulo H Pires
SH
de Oliveira
Paulo S Lopes
PS
Signore
Iskra A
IA
Colombo
Alicia
A
Concha
Miguel L
ML
Spengler
Tatjana S
TS
Bronner-Fraser
Marianne
M
Nobrega
Marcelo
M
Rosenthal
Nadia
N
Xavier-Neto
José
J
D000445:Aldehyde Oxidoreductases / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D017124:Conserved Sequence; D019143:Evolution, Molecular; D051538:Hepatocyte Nuclear Factor 1-alpha; D018398:Homeodomain Proteins; D007395:Interneurons; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D012097:Repressor Proteins; D013116:Spinal Cord / Q000502:physiology*; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors; D014212:Tretinoin / Q000502:physiology
C491272:Cdx1 protein, mouse; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D012097:Repressor Proteins; D051822:T Cell Transcription Factor 1; C490797:Tgif1 protein, mouse; D014157:Transcription Factors; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse