An essential role for retinoid signaling in anteroposterior neural patterning.
The vertebrate central nervous system (CNS) is induced by signals emanating from the dorsal mesoderm, or organizer, that divert the ectoderm away from an epidermal and towards a neural fate. Additional signals from the organizer pattern the neural ectoderm along the anteroposterior axis. We devised highly specific methods utilizing constitutively active or dominant negative receptors to evaluate the role of retinoids in neural patterning. Microinjection of these reagents either augments or reduces retinoid signaling in specific regions of the embryo. We show that increased receptor activity suppresses anterior neural structures while dominant negative receptors lead to anterior enhancement. Similarly, microinjection of the dominant negative receptor leads to the loss of posterior marker genes. We demonstrate that retinoid receptors comprise a critical component in neural posteriorization and are required for proper neuronal differentiation. These results support a quantitative role for retinoid signaling in regionalization of the CNS.
Blumberg
B
B
Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA. blumberg@axp1.salk.edu
Bolado
J
J
Moreno
T A
TA
Kintner
C
C
Evans
R M
RM
Papalopulu
N
N
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004475:Ectoderm / Q000166:cytology / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D004627:Embryonic Induction; D017930:Genes, Reporter; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D008845:Microinjections; D009420:Nervous System / Q000166:cytology / Q000196:embryology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014981:Xenopus / Q000196:embryology
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin