Activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the ophthalmic trigeminal placode.
Activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the ophthalmic trigeminal placode.
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DOI：
10.1016/j.ydbio.2008.11.032
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发表时间：
2009-02-15
影响因子：
2.7
通讯作者：
Baker, Clare V. H.
中科院分区：
文献类型：
--
作者：
Dude, Carolynn M.;Kuan, C. -Y. Kelly;Bradshaw, James R.;Greene, Nicholas D. E.;Relaix, Frederic;Stark, Michael R.;Baker, Clare V. H.
关键词：
脊椎动物颅神经源性基板是研究感觉神经发生控制的相对简单的模型系统。眼三叉神经（opV）基板，其最早的特异性标志物是配对结构域同源结构域转录因子Pax 3，在三叉神经节的眼叶中形成皮肤感觉神经元。我们以前表明，Pax 3在禽opV基板细胞的表达与规范和承诺的Pax 3+，皮肤感觉神经元的命运。Pax 3可以作为转录激活因子或抑制因子，这取决于细胞环境。我们使用小鼠Splotch 2 H突变体表明Pax 3对于opV基板细胞的正常神经元分化是必需的。使用编码Pax 3-Engrailed融合蛋白的电穿孔构建体，其抑制Pax 3靶基因，我们表明Pax 3靶基因的激活是必需的细胞自主在鸡opV基板细胞内表达opV基板标志物FGFR 4和Ngn 2，维持基板前标志物Eya 2，Pax 3本身的表达（表明Pax 3自动调节），神经元分化和分层。头部外胚层中Pax 3的错误表达足以诱导FGFR 4和Ngn 2表达，但神经元不分化，这表明额外的信号是使Pax 3+细胞分化为神经元所必需的。Pax 3在Pax 2+耳基板和上鳃基板中的错误表达也下调Pax 2并破坏耳泡闭合，表明Pax 3足以改变这些细胞的身份。总的来说，我们的研究结果表明，Pax 3靶基因的激活是必要的，但不足以在opV基板的神经发生。
Vertebrate cranial neurogenic placodes are relatively simple model systems for investigating the control of sensory neurogenesis. The ophthalmic trigeminal (opV) placode, for which the earliest specific marker is the paired domain homeodomain transcription factor Pax3, forms cutaneous sensory neurons in the ophthalmic lobe of the trigeminal ganglion. We previously showed that Pax3 expression in avian opV placode cells correlates with specification and commitment to a Pax3+, cutaneous sensory neuron fate. Pax3 can act as a transcriptional activator or repressor, depending on the cellular context. We show using mouse Splotch2H mutants that Pax3 is necessary for the normal neuronal differentiation of opV placode cells. Using an electroporation construct encoding a Pax3-Engrailed fusion protein, which represses Pax3 target genes, we show that activation of Pax3 target genes is required cell-autonomously within chick opV placode cells for expression of the opV placode markers FGFR4 and Ngn2, maintenance of the preplacodal marker Eya2, expression of Pax3 itself (suggesting that Pax3 autoregulates), neuronal differentiation and delamination. Mis-expression of Pax3 in head ectoderm is sufficient to induce FGFR4 and Ngn2 expression, but neurons do not differentiate, suggesting that additional signals are necessary to enable Pax3+ cells to differentiate as neurons. Mis-expression of Pax3 in the Pax2+ otic and epibranchial placodes also down-regulates Pax2 and disrupts otic vesicle closure, suggesting that Pax3 is sufficient to alter the identity of these cells. Overall, our results suggest that activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the opV placode.
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影响因子：
--
作者：
AUERBACH, R
通讯作者：
AUERBACH, R
DOI：
10.1073/pnas.90.2.532
发表时间：
1993-01-15
影响因子：
11.1
作者：
EPSTEIN, DJ;VOGAN, KJ;GROS, P
通讯作者：
GROS, P
影响因子：
2.7
作者：
Gradwohl, G;Fode, C;Guillemot, F
通讯作者：
Guillemot, F
影响因子：
16.2
作者：
KIOUSSI, C;GROSS, MK;GRUSS, P
通讯作者：
GRUSS, P
影响因子：
10.5
作者：
Bajard, Lola;Relaix, Frederic;Buckingham, Margaret E.
通讯作者：
Buckingham, Margaret E.