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Loss of Tbx2 delays optic vesicle invagination leading to small optic cups

Behesti, H; Papaioannou, VE; Sowden, JC; (2009) Loss of Tbx2 delays optic vesicle invagination leading to small optic cups. DEV BIOL , 333 (2) 360 - 372. 10.1016/j.ydbio.2009.06.026. Gold open access

Abstract

Tbx2 is a T-box transcription factor gene that is dynamically expressed in the presumptive retina during optic vesicle invagination. Several findings implicate Tbx2 in cell cycle regulation, including its overexpression in tumours and regulation of proliferation during heart development. We investigated the role of Tbx2 in optic cup formation by analysing mice with a targeted homozygous mutation in Tbx2. Loss of Tbx2 caused a reduced presumptive retinal volume due to increased apoptosis, and a delay in ventral optic vesicle invagination leading to the formation of small and abnormally shaped optic cups. Tbx2 is essential for maintenance, but not induction of expression of the dorsal retinal determinant, Tbx5, and acts downstream of Bmp4, a dorsally expressed gene implicated in human microphthalmia. The small retina showed a hypocellular ventral region, loss of Fgf15, normally expressed in proliferating central retinal cells, and increased numbers of mitotic cells in the dorsal region, indicating that Tbx2 is required for normal growth and development across the D-V axis. Dorsal expression of potential regulators of retinal growth, Cyp1b1 and Cx43, and the topographic guidance molecule ephrinB2, was increased, and intraretinal axons were disorganised resulting in a failure of optic nerve formation. Our data provide evidence that Tbx2 is required for proper optic cup formation and plays a critical early role in regulating regional retinal growth and the acquisition of shape during optic vesicle invagination. (C) 2009 Elsevier Inc. All rights reserved.

Type: Article
Title: Loss of Tbx2 delays optic vesicle invagination leading to small optic cups
Open access status: An open access publication
DOI: 10.1016/j.ydbio.2009.06.026
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC27356...
Keywords: Optic cup formation, Eye development, Retina, Tbx2, Optic vesicle, T-BOX GENES, RETINAL PROGENITOR PROLIFERATION, CYTOCHROME P4501B1 CYP1B1, TRANSCRIPTION FACTOR TBX2, GANGLION-CELL AXONS, EYE DEVELOPMENT, CHICK RETINA, OCULODENTODIGITAL DYSPLASIA, MURINE DEVELOPMENT, DORSOVENTRAL AXIS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
URI: http://discovery.ucl.ac.uk/id/eprint/153571
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