AP-2β is required for formation of the murine trabecular meshwork and Schlemm's canal.
AP-2β is required for formation of the murine trabecular meshwork and Schlemm's canal.
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DOI：
10.1016/j.exer.2020.108042
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发表时间：
2020-06
影响因子：
3.4
通讯作者：
West-Mays JA
中科院分区：
文献类型：
--
作者：
Akula M;Taiyab A;Deschamps P;Yee S;Ball AK;Williams T;West-Mays JA
以前，我们已经证明Tfap 2b，转录因子AP-2β编码基因，是正常小鼠眼睛发育所必需的。具体而言，神经嵴细胞（NCC）1及其衍生物，特别是眼周间充质（POM）中Tfap 2b的靶向缺失导致影响角膜和角组织的前段缺损。这些缺陷进一步与眼内压（IOP）升高相关。本研究调查了NCC中AP-2β缺失引起的胚胎和出生后POM细胞发育和分化的潜在变化，特别是使用Wnt 1Cre +/−; Tfap 2b-/lox; tdTomatolox/+小鼠（AP-2β神经嵴细胞敲除或AP-2β NCC KO）控制房水流出的结构。甲苯胺蓝染色切片和乙酸双氧铀和柠檬酸铅染色切片分别用于评估形态和超微结构。在胚胎第15.5天（E）、第18.5天（E）、出生后第1天（P）、第7天和第14天，使用磷酸化组蛋白H3（PH 3）、α-平滑肌肌动蛋白（αSMA）、肌球蛋白和内粘蛋白抗体以及TUNEL测定对KO和对照眼进行免疫组织化学。在NCC衍生的POM中有条件地缺失AP-2β导致在胚胎发生和出生后阶段出现的缺陷。突变体中敲除细胞的命运图显示，POM在胚胎发生过程中适当地迁移到眼睛中。然而，在出生后阶段的POM增殖的角度区域中观察到的突变体相比，对照组显着减少。这伴随着缺乏适当的小梁网和Schlemm管标记的表达。这是第一项研究表明AP-2β是小梁网和Schlemm管发育和分化所必需的。总之，这些缺陷可能导致先前在AP-2β NCC KO小鼠中报告的眼内压（IOP）升高。
Previously, we have shown that Tfap2b, the gene encoding transcription factor AP-2β, is needed for normal mouse eye development. Specifically, targeted loss of Tfap2b in neural crest cells (NCCs)1 and their derivatives, particularly the periocular mesenchyme (POM), resulted in anterior segment defects affecting the cornea and angle tissue. These defects were further associated with an increase in intraocular pressure (IOP). The present study investigates the underlying changes in embryonic and postnatal POM cell development and differentiation caused by loss of AP-2β in the NCCs, particularly in the structures that control aqueous outflow using Wnt1Cre+/−; Tfap2b-/lox; tdTomatolox/+ mice (AP-2β neural crest cell knockout or AP-2β NCC KO). Toluidine blue-stained sections and ultrathin sections stained with uranyl acetate and lead citrate were used to assess morphology and ultrastructure, respectively. Immunohistochemistry of KO and control eyes was performed at embryonic day (E) 15.5, E18.5, postnatal day (P) 1, P7 and P14 using phospho-histone H3 (PH3), α-smooth muscle actin (αSMA), myocilin and endomucin antibodies, as well as a TUNEL assay. Conditional deletion of AP-2β in the NCC-derived POM resulted in defects that appeared during both embryogenesis and postnatal stages. Fate mapping of the knockout cells in the mutants revealed that the POM migrated appropriately into the eye during embryogenesis. However, during postnatal stages a significant reduction in POM proliferation in the angle region was observed in the mutants compared to controls. This was accompanied by a lack of expression of appropriate trabecular meshwork and Schlemm’s canal markers. This is the first study to show that AP-2β is required for development and differentiation of the trabecular meshwork and Schlemm’s canal. Together, these defects likely contributed to the elevated intraocular pressure (IOP) previously reported in the AP-2β NCC KO mice.
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影响因子：
4.4
作者：
Chen L;Gage PJ
通讯作者：
Gage PJ
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
Schlemm的运河是一种独特的血管，具有通过新型发育过程形成的血管和淋巴表型的组合。
影响因子：
9.8
作者：
Kizhatil K;Ryan M;Marchant JK;Henrich S;John SW
通讯作者：
John SW
影响因子：
5
作者：
Raap, Mieke;Gronewold, Malte;Christgen, Matthias
通讯作者：
Christgen, Matthias
影响因子：
2.5
作者：
Napier, HRL;Kidson, SH
通讯作者：
Kidson, SH