Global analysis of RAR-responsive genes in the Xenopus neurula using cDNA microarrays.
Retinoid signaling is important for patterning the vertebrate hindbrain and midaxial regions. We recently showed that signaling through retinoic acid receptors (RARs) is essential for anteroposterior patterning along the entire body axis. To further investigate the mechanisms through which RARs act, we used microarray analysis to investigate the effects of modulating RAR activity on target gene expression. We identified 334 up-regulated genes (92% of which were validated), including known RA-responsive genes, known genes that have never been proposed as RA targets and many hypothetical and unidentified genes (n = 166). Sixty-seven validated down-regulated genes were identified, including known RA-responsive genes and anterior marker genes. The expression patterns of selected up-regulated genes (n = 45) were examined at neurula stages using whole-mount in situ hybridization. We found that most of these genes were expressed in the neural tube and many were expressed in anterior tissues such as neural crest, brain, eye anlagen, and cement gland. Some were expressed in tissues such as notochord, somites, pronephros, and blood islands, where retinoic acid (RA) plays established roles in organogenesis. Members of this set of newly identified RAR target genes are likely to play important roles in neural patterning and organogenesis under the control of RAR signaling pathways, and their further characterization will expand our understanding of RA signaling during development.
Arima
Kayo
K
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
Shiotsugu
Jason
J
Niu
Rong
R
Khandpur
Ritika
R
Martinez
Mayra
M
Shin
Yongchol
Y
Koide
Tetsuya
T
Cho
Ken W Y
KW
Kitayama
Atsushi
A
Ueno
Naoto
N
Chandraratna
Roshantha A S
RA
Blumberg
Bruce
B
D000818:Animals; D015152:Blotting, Northern; D019521:Body Patterning; D016000:Cluster Analysis; D015536:Down-Regulation; D005227:Fatty Acids / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism; D015854:Up-Regulation; D014981:Xenopus / Q000196:embryology*
D005227:Fatty Acids; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D013256:Steroids; D014212:Tretinoin