RETINOID SIGNALING AND THE GENERATION OF REGIONAL AND CELLULAR DIVERSITY IN THE EMBRYONIC MOUSE SPINAL-CORD

Retinoid-dependent gene expression accompanies the emergence of distin ct regions and cell classes in the mouse spinal cord around midgestati on. We asked whether changes in the expression of retinoid signaling m olecules and retinoid-responsive genes reflect the establishment of th is regional and cellular diversity. At E10.5, retinoic acid (RA) recep tors (RAR)alpha, RAR beta, the retinoid X receptor (RXR)gamma, cellula r RA binding protein (CRABP)I, CRAPBII, and cellular retinol binding p rotein (CRBP)I mRNAs are found throughout the entire anterior-posterio r (AP) axis of the cord, as is RA (Colbert et al. [1993] Proc. Natl. A cad. Sci. U.S.A. 90:6572-6576) and RA-sensitive transgene expression ( Balkan ct al. [1992] Proc. Natl, Acad, Sci, U.S.A, 89:3347-3351). At E 12.5, RA, transgene expression, and RAR beta become restricted to the cervical and lumbar cord. RAR beta, CRABPI, and RXR gamma, however, ar e found throughout the AP extent. CRABPII and CRBPI, although expanded within the cervical and lumbar regions, are also found throughout the AP axis. Thus, several retinoid signaling molecules continue to be ex pressed beyond distinct regions of the spinal cord where RA is availab le and some RA-responsive genes are either restricted or enhanced. Exo genous RA can activate a more widespread response resulting in ectopic transgene and RAR beta expression in the thoracic and sacral cord, No t all RA-sensitive genes, however, respond; CRABPII and CRBPI expressi on patterns are unchanged, Finally, not every cell within the normal o r exogenously induced domains of RA-dependent gene expression responds to RA, nor does every cell express RA receptors or binding proteins. Thus, regional and cellular differences in the distribution of the kno wn retinoid receptors and binding proteins do not predict absolutely w here or whether retinoid sensitive genes will be expressed or where re tinoids will be available in the developing spinal cord, Instead, reti noid-mediated gene expression in the cervical and lumbar cord seems to reflect retinoid responses that rely both on the local availability o f retinoids, the identity of the responding gene, and an indeterminate array of retinoid signaling molecules. (C) 1995 Wiley-Liss, Inc.