Loss of orphan nuclear receptor GCNF function disrupts forebrain development and the establishment of the isthmic organizer.
The isthmic organizer, which is located at the midbrain-hindbrain boundary, is important for midbrain development. The mechanism by which the development of the organizer is initiated and maintained is not well understood. Inactivation of the gene encoding the orphan nuclear receptor, GCNF, diminishes the expression of secreted signaling molecules, Fgf8 and Wnt1, the paired box genes Pax2/5, En1/2, and homeodomain transcription factor Gbx2; all of which are essential for isthmic organizer function. In addition, full neuronal differentiation is not observed in the midbrain region of GCNF-/- embryos. Increased cell death may contribute to the loss of midbrain structure in GCNF-/- embryos. These results indicate that GCNF is required for establishment of the isthmic organizer, thereby regulating the midbrain development.
Chung
Arthur C-K
AC
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xu
Xueping
X
Niederreither
Karen A
KA
Cooney
Austin J
AJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D004475:Ectoderm / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008636:Mesencephalon / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000166:cytology; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1; D020897:Organizers, Embryonic / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D051857:Otx Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D016548:Prosencephalon / Q000002:abnormalities* / Q000196:embryology* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019170:Somites / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C539954:Nr6a1 protein, mouse; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; C425468:Spry1 protein, mouse; D051524:Fibroblast Growth Factor 8