Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer

Abstract

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.