Retinoic acid regulates the morphological development of sympathetic neurons.
Interactions between all-trans-retinoic acid (RA) and bone morphogenetic proteins (BMPs) affect the expression of neurotrophin receptors in sympathetic neurons (Kobayashi et al., 1998). In this study, we examined the possibility that similar interactions might regulate the morphological development of these neurons. Under control conditions, embryonic rat sympathetic neurons formed axons but not dendrites; cells exposed to RA had a similar appearance. Profuse dendritic growth was observed upon exposure to BMP-7, and this was reduced by approximately 70% by RA. This inhibitory effect of RA was mediated primarily by retinoic acid receptors (RARs) and it exhibited substantial specificity because it was not associated with changes in either axonal elongation or cell survival. Moreover, mRNAs for enzymes required for synthesis of RA were expressed in the sympathetic neurons and retinoid activity was released from superior cervical ganglia. These observations suggest that retinoids may function as endogenous morphogens and regulate neural cell shape and polarity in developing sympathetic ganglia.
Chandrasekaran
V
V
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Zhai
Y
Y
Wagner
M
M
Kaplan
P L
PL
Napoli
J L
JL
Higgins
D
D
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000072467:Cytochrome P450 Family 2; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000378:metabolism; D050697:Retinal Dehydrogenase; D047488:Retinoid X Receptors; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism; D016212:Transforming Growth Factor beta; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014801:Vitamin A; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; C504568:Cyp2d1 protein, rat; D000072467:Cytochrome P450 Family 2; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase