UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Gene. 2012 Nov 1;509(1):93-103. doi: 10.1016/j.gene.2012.08.001. Epub 2012 Aug 15.
The development of stratified retinal cell architecture is highly conserved in all vertebrates, implying that a common fundamental molecular mechanism is involved in the generation of the organized retina. However, the detailed molecular mechanisms of retinal development are not fully understood. Here we have identified the Xenopus ortholog of prune and show that it is expressed in both differentiating and differentiated retinal domains during development. Interestingly, these spatial and temporal expression patterns coincide with the expression of prune binding partners, the NM23 family members. Overexpression of prune in retinal precursor cells significantly increases the ratio of Müller glial cells as observed by modulation of NM23 activity (Mochizuki et al., 2009). However, a mutated form of prune that has replacement of four aspartate (D) residues (D'Angelo et al., 2004), essential for phosphodiesterase activity, does not exhibit gliogenic activity. Our observations suggest that Xenopus prune may regulate Müller gliogenesis through phosphodiesterase-mediated regulation of NM23 family members.
分层视网膜细胞结构的发育在所有脊椎动物中高度保守,这意味着在组织视网膜的产生过程中涉及到一个共同的基本分子机制。然而,视网膜发育的详细分子机制尚不完全清楚。在这里,我们鉴定了爪蟾的 prune 同源物,并表明它在发育过程中在分化和分化的视网膜区域表达。有趣的是,这些空间和时间表达模式与 prune 结合伴侣 NM23 家族成员的表达相吻合。在视网膜前体细胞中过表达 prune 会显著增加 Müller 胶质细胞的比例,这可以通过 NM23 活性的调节来观察到(Mochizuki 等人,2009)。然而,一种具有替换四个天冬氨酸(D)残基(D'Angelo 等人,2004)的 prune 的突变形式,对于磷酸二酯酶活性是必需的,不表现出神经胶质生成活性。我们的观察表明,爪蟾 prune 可能通过磷酸二酯酶介导的 NM23 家族成员的调节来调节 Müller 神经胶质发生。