Anteriorization of CRABP-I expression by retinoic acid in the developing mouse central nervous system and its relationship to teratogenesis.
We have investigated the role that cellular retinoic acid binding protein I (CRABP-I) may play in the development of the murine hindbrain. Since the central nervous system (CNS) represents a major site of the teratogenic action of retinoic acid (RA), we have also determined the effects of exposure of high levels of RA on CRABP-I expression within the CNS. Expression of CRABP-I can first be detected within the presumptive hindbrain of presomitic mouse embryos and later also appears in neural crest cells and neural crest derivatives; it is thus tissue specific at these early stages. Exposure of 7.75-day mouse embryos to RA induces two phenotypes: one is externally normal and the other is exencephalic. In the exencephalic embryos we show that there is abnormal crest migration, a fusion of the trigeminal and facial-acoustic ganglia, a rostral and lateral shift of the otic vesicle, and a loss of hindbrain rhombomeres. Furthermore, and in contrast to in vitro studies, we demonstrate that CRABP-I appears to be up-regulated in both phenotypes of mouse embryos treated with RA and that this up-regulation is accompanied by an anteriorization of its expression within the nervous system. This new CRABP-I expression domain thus retains its tissue specificity. The role that CRABP-I may play in normal development of the hindbrain and in teratogenesis and the similarity of these results to those obtained with various Hox genes are discussed.
Leonard
L
L
Developmental Biology Research Centre, King's College London, United Kingdom.
Horton
C
C
Maden
M
M
Pizzey
J A
JA
D000818:Animals; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D005314:Embryonic and Fetal Development; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D013724:Teratoma / Q000209:etiology; D014212:Tretinoin / Q000009:adverse effects / Q000494:pharmacology*; D015854:Up-Regulation
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014212:Tretinoin