The germ cell nuclear factor is required for retinoic acid signaling during Xenopus development
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The germ cell nuclear factor is required for retinoic acid signaling during Xenopus development. / Barreto, Guillermo; Borgmeyer, Uwe; Dreyer, Christine.
in: MECH DEVELOP, Jahrgang 120, Nr. 4, 04.2003, S. 415-28.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The germ cell nuclear factor is required for retinoic acid signaling during Xenopus development
AU - Barreto, Guillermo
AU - Borgmeyer, Uwe
AU - Dreyer, Christine
PY - 2003/4
Y1 - 2003/4
N2 - The germ cell nuclear factor (GCNF, NR6A1) is a nuclear orphan receptor that functions as a transcriptional repressor and is transiently expressed in mammalian carcinoma cells during retinoic acid (RA) induced neuronal differentiation. During Xenopus laevis development, the spatiotemporal expression pattern of embryonic GCNF (xEmGCNF) suggests a role in anteroposterior specification of the neuroectoderm. Here, we show that RA treatment of Xenopus embryos enhances xEmGCNF expression. Moreover, we present evidence for the relevance of this finding in the context of primary neurogenesis and hindbrain development. During early development of the central nervous system, RA signals promote posterior transformation of the neuroectoderm and increase the number of cells undergoing primary neurogenesis. Our loss-of-function analyses using a xEmGCNF-specific morpholino antisense oligonucleotide indicate that xEmGCNF is required for the effect of RA on primary neurogenesis. This may be caused by transcriptional regulation of the gene encoding the RA-degrading enzyme CYP26, since this gene is derepressed after depletion of xEmGCNF and an antimorph of xEmGCNF directly activates transcription of CYP26, also in absence of protein synthesis. The effect of xEmGCNF knockdown on hindbrain patterning is similar to conditions of reduced RA signaling, which may be caused by a reduction of RAR gamma expression specifically in the presumptive hindbrain.
AB - The germ cell nuclear factor (GCNF, NR6A1) is a nuclear orphan receptor that functions as a transcriptional repressor and is transiently expressed in mammalian carcinoma cells during retinoic acid (RA) induced neuronal differentiation. During Xenopus laevis development, the spatiotemporal expression pattern of embryonic GCNF (xEmGCNF) suggests a role in anteroposterior specification of the neuroectoderm. Here, we show that RA treatment of Xenopus embryos enhances xEmGCNF expression. Moreover, we present evidence for the relevance of this finding in the context of primary neurogenesis and hindbrain development. During early development of the central nervous system, RA signals promote posterior transformation of the neuroectoderm and increase the number of cells undergoing primary neurogenesis. Our loss-of-function analyses using a xEmGCNF-specific morpholino antisense oligonucleotide indicate that xEmGCNF is required for the effect of RA on primary neurogenesis. This may be caused by transcriptional regulation of the gene encoding the RA-degrading enzyme CYP26, since this gene is derepressed after depletion of xEmGCNF and an antimorph of xEmGCNF directly activates transcription of CYP26, also in absence of protein synthesis. The effect of xEmGCNF knockdown on hindbrain patterning is similar to conditions of reduced RA signaling, which may be caused by a reduction of RAR gamma expression specifically in the presumptive hindbrain.
KW - Animals
KW - Blotting, Western
KW - Brain
KW - Cycloheximide
KW - Cytochrome P-450 Enzyme System
KW - DNA-Binding Proteins
KW - Galactosides
KW - Gene Expression Regulation, Developmental
KW - In Situ Hybridization
KW - Indoles
KW - Neurons
KW - Nuclear Receptor Subfamily 6, Group A, Member 1
KW - Protein Biosynthesis
KW - Protein Synthesis Inhibitors
KW - RNA, Messenger
KW - Receptors, Cytoplasmic and Nuclear
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Signal Transduction
KW - Time Factors
KW - Tretinoin
KW - Xenopus
M3 - SCORING: Journal article
C2 - 12676320
VL - 120
SP - 415
EP - 428
JO - MECH DEVELOP
JF - MECH DEVELOP
SN - 0925-4773
IS - 4
ER -