Gbx2 directly restricts Otx2 expression to forebrain and midbrain, competing with class III POU factors.

Molecular and Cellular Biology
Fumitaka InoueS Aizawa

Abstract

Otx2 plays essential roles in rostral brain development, and its counteraction with Gbx2 has been suggested to determine the midbrain-hindbrain boundary (MHB) in vertebrates. We previously identified the FM enhancer that is conserved among vertebrates and drives Otx2 transcription in forebrain/midbrain from the early somite stage. In this study, we found that the POU homeodomain of class III POU factors (Brn1, Brn2, Brn4, and Oct6) associates with noncanonical target sequence TAATTA in the FM enhancer. MicroRNA-mediated knockdown of Brn2 and Oct6 diminished the FM enhancer activity in anterior neural progenitor cells (NPCs) differentiated from P19 cells. The class III POU factors associate with the FM enhancer in forebrain and midbrain but not in hindbrain. We also demonstrated that the Gbx2 homeodomain recognizes the same target TAATTA in the FM enhancer, and Gbx2 associates with the FM enhancer in hindbrain. Gbx2 misexpression in the anterior NPCs repressed the FM enhancer activity and inhibited Brn2 association with the enhancer, whereas Gbx2 knockdown caused ectopic Brn2 association in the posterior NPCs. These results suggest that class III POU factors and Gbx2 share the same target site, TAATTA, in the FM enhancer and tha...Continue Reading

References

Jun 1, 1994·Genes & Development·R A RuppH Weintraub
Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A F Schier, W J Gehring
Mar 1, 1993·Genes & Development·J G PattonB Nadal-Ginard
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·H OkazawaM M Mouradian
Jan 1, 1996·Progress in Biophysics and Molecular Biology·M Billeter
Oct 10, 1998·Mechanisms of Development·K Niss, A Leutz
Oct 10, 1998·Mechanisms of Development·H Shamim, I Mason
Dec 16, 1998·The Journal of Biological Chemistry·J M RheeE E Turner
Mar 8, 2000·Mechanisms of Development·T KatahiraH Nakamura
May 29, 2000·Trends in Genetics : TIG·A Simeone
Jun 8, 2000·Developmental Dynamics : an Official Publication of the American Association of Anatomists·G Hauptmann, T Gerster
Nov 7, 2000·Current Opinion in Cell Biology·A L JoynerS Millet
Dec 18, 2001·Mechanisms of Development·Ella TourAbraham Fainsod
Feb 19, 2002·Mechanisms of Development·Ella TourAbraham Fainsod
Feb 23, 2002·Science·Robert J McEvillyMichael G Rosenfeld
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Silvia MarettoStefano Piccolo
Aug 20, 2003·Development·Shigeyasu NakaiTetsuo Noda
Oct 28, 2003·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Hiroshi KikutaKyo Yamasu
Jun 18, 2004·Development·Daisuke KurokawaShinichi Aizawa
Oct 25, 2006·Molecular and Cellular Biology·Thomas HeimbucherThomas Czerny
Dec 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Daisuke KurokawaShinichi Aizawa
Mar 3, 2007·The EMBO Journal·Nobuyoshi TakasakiShinichi Aizawa

❮ Previous
Next ❯

Citations

Oct 9, 2013·EvoDevo·Linda Z HollandJr-Kai Yu
Jul 16, 2014·Neuroscience Research·Takuma Kumamoto, Carina Hanashima
Dec 17, 2014·Frontiers in Psychology·Cedric Boeckx, Antonio Benítez-Burraco
Jul 21, 2016·Development·Giacomo MasserdottiMagdalena Götz
Aug 22, 2017·Frontiers in Neuroanatomy·Holly C GibbsArne C Lekven
Dec 18, 2019·The Journal of Clinical Investigation·Ryusaku MatsumotoYutaka Takahashi
Nov 30, 2018·Frontiers in Neuroanatomy·Claudia M García-PeñaAlfredo Varela-Echavarría
Nov 3, 2016·Genome Research·Marco-Antonio Mendoza-ParraHinrich Gronemeyer
Dec 17, 2020·Journal of Developmental Biology·David A RoeselerSamuel T Waters

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.