Age-dependent retinoic acid regulation of gene expression distinguishes the cervical, thoracic, lumbar, and sacral spinal cord regions during development

We evaluated whether differences in the availability of retinoic acid (RA) establish distinct patterns of RA-dependent gene expresion in the embryonic mouse thoracic/sacral versus cervical/lumbar spinal cord regions. Exogenou s RA elicits ectopic expression of an RA-activated transgene and the RA rec eptor beta in the dorsal thoracic and sacral cord in mice at embryonic day (E) 12.5, but not E14.5. This age-dependent regulation is cell autonomous a nd is not accompanied by changes in expression patterns of several retinoid receptors, binding proteins, or the SMRT nuclear corepressor. Instead, thi s change apparently reflects the loss of endogenous RA in the dorsal thorac ic-and sacral cord between E12.5 and E14.5. Thus, chronic exposure to exoge nous RA between E11.5 and E13.5 restores ectopic RA-mediated gene expressio n. These observations suggest that the local availability of RA establishes absolute differences in gene expression that distinguish the thoracic and sacral co rd from the cervical and lumbar cord during midgestation.