BMP receptor 1b is required for axon guidance and cell survival in the developing retina

BMP receptor 1b is required for axon guidance and cell survival in the developing retina
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DOI:
10.1016/s0012-1606(02)00115-x
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发表时间:
2003-04-01
影响因子:
2.7
通讯作者:
Reh, T
Reh, T
中科院分区:
生物学3区
文献类型:
--
作者:
Liu, J;Wilson, S;Reh, T

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以前的工作已经证明了BMP在眼睛发育中的重要性。在小鼠中进行的功能丧失研究,在Bmp7或Bmp4基因中进行靶向缺失,表明这些分子对早期眼睛发育至关重要。这个家庭的几个成员的背腹表达模式的不对称性的基础上,有人提出,这些分子是关键的某些方面的背腹图案的眼睛,然而,它一直难以测试这一假设,因为早期的要求骨形成蛋白在眼睛的发展。因此,我们通过使用靶向缺失来检查BMP受体之一BntprIb的缺失对眼睛发育的影响。我们发现BmprIb在胚胎发育期间仅在腹侧视网膜中表达,并且是正常腹侧神经节细胞轴突靶向视神经乳头所需的。在BmprIb基因靶向缺失的小鼠中,许多来自腹侧神经节细胞的轴突未能进入视神经乳头,而是在该区域突然转弯。这些小鼠的第二个表型是在出生后发育的不同阶段,在神经发生结束时,视网膜内细胞凋亡显著升高。因此,我们的研究结果表明,在哺乳动物视网膜发育的BntprIb两个不同的要求。(C)2003 Elsevier Science(美国)。All rights reserved.
Previous work has documented the importance of BMPs in eye development. Loss-of-function studies in mice, with targeted deletions in either the Bmp7 or Bmp4 genes, have shown that these molecules are critical for early eye development. On the basis of the asymmetry in the dorsal-ventral expression patterns of several members of this family, it has been proposed that these molecules are critical for some aspect of dorsal-ventral patterning in the eye; however, it has been difficult to test this hypothesis because of the early requirement for BMPs in eye development. We have therefore examined the effects of loss of one of the BMP receptors, the BntprIb, on the development of the eye by using targeted deletion. We have found that BmprIb is expressed exclusively in the ventral retina during embryonic development and is required for normal ventral ganglion cell axon targeting to the optic nerve head. In mice with a targeted deletion of the BmprIb gene, many axons arising from the ventrally located ganglion cells fail to enter the optic nerve head, and instead, make abrupt turns in this region. A second phenotype in these mice is a significantly elevated inner retinal apoptosis during a distinct phase of postnatal development, at the end of neurogenesis. Our results therefore show two distinct requirements for BntprIb in mammalian retinal development. (C) 2003 Elsevier Science (USA). All rights reserved.