Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer.
We examined whether Gbx2 is required after embryonic day 9 (E9) to repress Otx2 in the cerebellar anlage and position the midbrain/hindbrain organizer. In contrast to Gbx2 null mutants, mice lacking Gbx2 in rhombomere 1 (r1) after E9 (Gbx2-CKO) are viable and develop a cerebellum. A Gbx2-independent pathway can repress Otx2 in r1 after E9. Mid/hindbrain organizer gene expression, however, continues to be dependent on Gbx2. We found that Fgf8 expression normally correlates with the isthmus where cells undergo low proliferation and that in Gbx2-CKO mutants this domain is expanded. We propose that Fgf8 permits lateral cerebellar development through repression of Otx2 and also suppresses medial cerebellar growth in Gbx2-CKO embryos. Our work has uncovered distinct requirements for Gbx2 during cerebellum formation and provided a model for how a transcription factor can play multiple roles during development.
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002531:Cerebellum / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051857:Otx Transcription Factors; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins
C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; C080331:Hoxa3 protein, mouse; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C513181:gbx2 protein, zebrafish; C489831:hoxa2b protein, zebrafish