Loss of Tbx2 delays optic vesicle invagination leading to small optic cups.
Loss of Tbx2 delays optic vesicle invagination leading to small optic cups.
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DOI：
10.1016/j.ydbio.2009.06.026
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发表时间：
2009-09-15
影响因子：
2.7
通讯作者：
Sowden, Jane C.
中科院分区：
文献类型：
--
作者：
Behesti, Hourinaz;Papaioannou, Virginia E.;Sowden, Jane C.
Tbx2是一个T-box转录因子基因，在视泡内陷时，在假定的视网膜中动态表达。一些发现表明Tbx2参与了细胞周期的调节，包括它在肿瘤中的过度表达和心脏发育过程中的增殖调节。我们通过分析Tbx2中具有靶向纯合突变的小鼠，研究了Tbx2在视杯形成中的作用。Tbx2的缺失导致视网膜体积减少，这是由于细胞凋亡增加，延缓腹侧视泡内陷，导致小而形状异常的视杯的形成。Tbx2对视网膜背侧决定基因Tbx5的表达是必需的，但不是诱导表达，它作用于Bmp4的下游，Bmp4是一种与人类小眼球有关的背部表达的基因。小视网膜表现为腹侧细胞减少，Fgf15缺失，正常表达于增殖的中央视网膜细胞，背侧有丝分裂细胞增多，提示Tbx2是D-V轴正常生长发育所必需的。潜在的视网膜生长调节因子CYP1B1和Cx43以及地形图引导分子ewitinb2的背部表达增加，视网膜内轴突组织紊乱，导致视神经形成失败。我们的数据提供了证据，证明Tbx2是正常视杯形成所必需的，并在调节区域视网膜生长和视泡内陷期间获得形状方面发挥关键的早期作用。
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 intra-retinal 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.
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DOI：
10.1098/rspb.1985.0021
发表时间：
1985-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DRAGER, UC
通讯作者：
DRAGER, UC
影响因子：
--
作者：
Behesti H;Holt JK;Sowden JC
通讯作者：
Sowden JC
影响因子：
5.3
作者：
Becker, DL;Mobbs, P
通讯作者：
Mobbs, P
影响因子：
5.3
作者：
Carreira, S;Dexter, TJ;Goding, CR
通讯作者：
Goding, CR
影响因子：
10.5
作者：
Bertuzzi, S;Hindges, R;Lemke, G
通讯作者：
Lemke, G