The LIM-Homeodomain transcription factor Islet-1 is required for the development of sympathetic neurons and adrenal chromaffin cells.
The LIM-Homeodomain transcription factor Islet-1 is required for the development of sympathetic neurons and adrenal chromaffin cells.
复制标题
DOI：
10.1016/j.ydbio.2013.04.027
复制
发表时间：
2013-08-15
影响因子：
2.7
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Huber K;Narasimhan P;Shtukmaster S;Pfeifer D;Evans SM;Sun Y
胰岛-1是一种LIM同源结构域转录因子，对不同的神经元和非神经元细胞群的发育具有重要作用。我们在这里表明，在交感-肾上腺细胞谱系的细胞中，Islet-1在基因上作用于PHOX2B下游，并且在小鼠胚胎中，交感神经元和嗜铬细胞的发育受到损害，有条件地删除了由wnt1启动子控制的Islet-1。从胰岛-1缺陷小鼠胚胎初级交感神经节中正确表达泛神经元和儿茶酚胺能亚型特异性基因表明，胰岛-1对交感肾上腺细胞的初始分化不是必需的。然而，我们的数据表明，交感神经元前体随后的存活以及它们向TrkA表达神经元的分化依赖于Islet-1的功能。与脊髓感觉神经元相比，胰岛-1缺陷小鼠的交感神经元没有表现出正常存在于中枢神经系统的基因的异位表达。在胰岛-1缺陷小鼠胚胎中，与交感神经元相比，嗜铬细胞数量仅轻微减少，但肾上腺素合成酶PNMT的启动被取消，嗜铬粒蛋白A的表达水平降低。基因芯片分析显示，胰岛-1缺陷小鼠发育中的嗜铬细胞TH、DBH和转录因子PHOX2B、MASH-1、Hand2、GATA3和Insm1的表达水平正常，而转录因子GATA2、Hand1和AP-2β的表达水平显著降低。总之，我们的数据表明，Islet-1对交感肾上腺细胞的初始分化不是必需的，但对交感神经元和嗜铬细胞的正确后续发育具有重要作用。
Islet-1 is a LIM-Homeodomain transcription factor with important functions for the development of distinct neuronal and non-neuronal cell populations. We show here that Islet-1 acts genetically downstream of Phox2B in cells of the sympathoadrenal cell lineage and that the development of sympathetic neurons and chromaffin cells is impaired in mouse embryos with a conditional deletion of Islet-1 controlled by the wnt1 promotor. Islet-1 is not essential for the initial differentiation of sympathoadrenal cells, as indicated by the correct expression of pan-neuronal and catecholaminergic subtype specific genes in primary sympathetic ganglia of Islet-1 deficient mouse embryos. However, our data indicate that the subsequent survival of sympathetic neuron precursors and their differentiation towards TrkA expressing neurons depends on Islet-1 function. In contrast to spinal sensory neurons, sympathetic neurons of Islet-1 deficient mice did not display ectopic expression of genes normally present in the CNS. In Islet-1 deficient mouse embryos the numbers of chromaffin cells were only mildly reduced, in contrast to that of sympathetic neurons, but the initiation of the adrenaline synthesizing enzyme PNMT was abrogated and the expression level of chromogranin A was diminished. Microarray analysis revealed that developing chromaffin cells of Islet-1 deficient mice displayed normal expression levels of TH, DBH and the transcription factors Phox2B, Mash-1, Hand2, Gata3 and Insm1, but the expression levels of the transcription factors Gata2 and Hand1, and AP-2β were significantly reduced. Together our data indicate that Islet-1 is not essentially required for the initial differentiation of sympathoadrenal cells, but has an important function for the correct subsequent development of sympathetic neurons and chromaffin cells.
登录
查看更多内容
影响因子：
3.3
作者：
Glassmann, A.;Topka, S.;Schilling, K.
通讯作者：
Schilling, K.
影响因子：
2.6
作者：
Ernsberger, U;Patzke, H;Rohrer, H
通讯作者：
Rohrer, H
DOI：
10.1523/jneurosci.0901-11.2011
发表时间：
2011-07-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dykes IM;Tempest L;Lee SI;Turner EE
通讯作者：
Turner EE
影响因子：
2.7
作者：
Hendershot, Tyler J.;Liu, Hongbin;Howard, Marthe J.
通讯作者：
Howard, Marthe J.
影响因子：
3.7
作者：
Golzio C;Havis E;Daubas P;Nuel G;Babarit C;Munnich A;Vekemans M;Zaffran S;Lyonnet S;Etchevers HC
通讯作者：
Etchevers HC