The mechanism of lens placode formation: a case of matrix-mediated morphogenesis.
The mechanism of lens placode formation: a case of matrix-mediated morphogenesis.
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DOI：
10.1016/j.ydbio.2011.04.008
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发表时间：
2011-07-01
影响因子：
2.7
通讯作者：
Beebe DC
中科院分区：
文献类型：
--
作者：
Huang J;Rajagopal R;Liu Y;Dattilo LK;Shaham O;Ashery-Padan R;Beebe DC
尽管基板是组织内陷的普遍存在的前体，但基板形成的机制尚未建立，并且尚未测试基板形成对随后内陷的要求。早期在鸡胚胎中的测量支持这样的观点，即透镜基板形成的发生是因为视泡和表面外胚层之间的细胞外基质（ECM）阻止了预期的透镜细胞扩散。在该限制区域内的持续细胞增殖被认为引起细胞拥挤，导致细胞伸长（基板形成）。这种观点表明，持续的细胞增殖和粘附到视泡和表面外胚层之间的ECM足以解释透镜基板的形成。为了检验这一“限制性扩张假说”的预测，我们首先证实了鸡胚胎中伴随透镜基板形成的细胞事件也发生在小鼠胚胎中。然后，我们表明，失败的透镜基板形成时的转录因子，Pax 6是有条件地删除在表面外胚层与大大减少积累的ECM之间的视泡和外胚层和降低水平的转录编码成分的ECM。与“限制性扩张假说”的雅阁一致，Pax 6缺失的外胚层扩张，而不是被限制在一个恒定的区域。作为进一步的测试，我们通过删除Fn 1来破坏ECM，Fn 1是基质组装和细胞-基质粘附所必需的。在Pax 6CKO胚胎中，Fn 1CKO透镜外胚层扩张，而不是被限制在一个固定的区域，透镜基板没有形成。Fn 1 CKO胚胎中的外胚层细胞表达透镜诱导的标记物，并重组其细胞骨架，如在野生型外胚层，但没有内陷，这表明基板形成确立了内陷的最低机械要求。
Although placodes are ubiquitous precursors of tissue invagination, the mechanism of placode formation has not been established and the requirement of placode formation for subsequent invagination has not been tested. Earlier measurements in chicken embryos supported the view that lens placode formation occurs because the extracellular matrix (ECM) between the optic vesicle and the surface ectoderm prevents the prospective lens cells from spreading. Continued cell proliferation within this restricted area was proposed to cause cell crowding, leading to cell elongation (placode formation). This view suggested that continued cell proliferation and adhesion to the ECM between the optic vesicle and the surface ectoderm was sufficient to explain lens placode formation. To test the predictions of this “restricted expansion hypothesis,” we first confirmed that the cellular events that accompany lens placode formation in chicken embryos also occur in mouse embryos. We then showed that the failure of lens placode formation when the transcription factor, Pax6 was conditionally deleted in the surface ectoderm was associated with greatly diminished accumulation of ECM between the optic vesicle and ectoderm and reduced levels of transcripts encoding components of the ECM. In accord with the “restricted expansion hypothesis,” the Pax6-deleted ectoderm expanded, rather than being constrained to a constant area. As a further test, we disrupted the ECM by deleting Fn1, which is required for matrix assembly and cell-matrix adhesion. As in Pax6CKO embryos, the Fn1CKO lens ectoderm expanded, rather than being constrained to a fixed area and the lens placode did not form. Ectoderm cells in Fn1CKO embryos expressed markers of lens induction and reorganized their cytoskeleton as in wild type ectoderm, but did not invaginate, suggesting that placode formation establishes the minimal mechanical requirements for invagination.
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影响因子：
1.5
作者：
Naiche, L. A.;Papaioannou, Virginia E.
通讯作者：
Papaioannou, Virginia E.
影响因子：
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Corbett, SA;Lee, L;Schwarzbauer, JE
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Gruss, P
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作者：
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作者：
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