TY - JOUR
T1 - Complementary domains of retinoic acid production and degradation in the early chick embryo
AU - Swindell, Eric C.
AU - Thaller, Christina
AU - Sockanathan, Shanthini
AU - Petkovich, Martin
AU - Jessell, Thomas M.
AU - Eichele, Gregor
N1 - Funding Information:
We thank Dr. Sammuel Pfaff for the cloning of a chick RALDH-2 fragment, Dr. Susan Mackem for supplying a chick limb bud cDNA library, and Dr. Kerby Oberg for comments on the manuscript. This work was supported by the National Institute of Health (G.E., C.T., T.M.J.). T.M.J. is an Investigator of the Howard Hughes Medical Institute.
PY - 1999/12/1
Y1 - 1999/12/1
N2 - Excess retinoids as well as retinoid deprivation cause abnormal development, suggesting that retinoid homeostasis is critical for proper morphogenesis. RALDH-2 and CYP26, two key enzymes that carry out retinoic acid (RA) synthesis and degradation, respectively, were cloned from the chick and show significant homology with their orthologs in other vertebrates. Expression patterns of RALDH-2 and CYP26 genes were determined in the early chick embryo by in situ hybridization. During gastrulation and neurulation RALDH-2 and CYP26 were expressed in nonoverlapping regions, with RALDH-2 transcripts localized to the presumptive presomitic and lateral plate mesoderm and CYP26 mRNA to the presumptive mid- and forebrain. The two domains of expression were separated by an approximately 300-μm-wide gap, encompassing the presumptive hindbrain. In the limb region, a similar spatial segregation of RALDH-2 and CYP26 expression was found at stages 14 and 15. Limb region mesoderm expressed RALDH-2, whereas the overlying limb ectoderm expressed CYP26. RA-synthesizing and -degrading enzymatic activities were measured biochemically in regions expressing RALDH-2 or CYP26. Regions expressing RALDH-2 generated RA efficiently from precursor retinal but degraded RA only inefficiently. Conversely, tissue expressing CYP26 efficiently degraded but did not synthesize RA. Localized regions of RA synthesis and degradation mediated by these two enzymes may therefore provide a mechanism to regulate RA homeostasis spatially in vertebrate embryos.
AB - Excess retinoids as well as retinoid deprivation cause abnormal development, suggesting that retinoid homeostasis is critical for proper morphogenesis. RALDH-2 and CYP26, two key enzymes that carry out retinoic acid (RA) synthesis and degradation, respectively, were cloned from the chick and show significant homology with their orthologs in other vertebrates. Expression patterns of RALDH-2 and CYP26 genes were determined in the early chick embryo by in situ hybridization. During gastrulation and neurulation RALDH-2 and CYP26 were expressed in nonoverlapping regions, with RALDH-2 transcripts localized to the presumptive presomitic and lateral plate mesoderm and CYP26 mRNA to the presumptive mid- and forebrain. The two domains of expression were separated by an approximately 300-μm-wide gap, encompassing the presumptive hindbrain. In the limb region, a similar spatial segregation of RALDH-2 and CYP26 expression was found at stages 14 and 15. Limb region mesoderm expressed RALDH-2, whereas the overlying limb ectoderm expressed CYP26. RA-synthesizing and -degrading enzymatic activities were measured biochemically in regions expressing RALDH-2 or CYP26. Regions expressing RALDH-2 generated RA efficiently from precursor retinal but degraded RA only inefficiently. Conversely, tissue expressing CYP26 efficiently degraded but did not synthesize RA. Localized regions of RA synthesis and degradation mediated by these two enzymes may therefore provide a mechanism to regulate RA homeostasis spatially in vertebrate embryos.
UR - http://www.scopus.com/inward/record.url?scp=0032714961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032714961&partnerID=8YFLogxK
U2 - 10.1006/dbio.1999.9487
DO - 10.1006/dbio.1999.9487
M3 - Article
C2 - 10588879
AN - SCOPUS:0032714961
SN - 0012-1606
VL - 216
SP - 282
EP - 296
JO - Developmental biology
JF - Developmental biology
IS - 1
ER -