Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype
Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype
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DOI：
10.1242/dev.00816
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发表时间：
2003-12-01
期刊：
影响因子：
4.6
通讯作者：
Driever, W
中科院分区：
文献类型：
--
作者：
Holzschuh, J;Barrallo-Gimeno, A;Driever, W
Tfap 2a是在许多不同细胞类型中表达的转录激活因子，包括神经元、神经嵴衍生物和表皮。我们发现，突变在斑马鱼基因座以前称为勃朗峰（MOB）或锁颌（低）编码tfap 2a。突变体表型表明，tfap 2a是必不可少的后脑去甲肾上腺素能（NA）神经元的蓝斑，髓质和最后区，以及交感神经元NA神经元，上鳃基板衍生内脏感觉神经节，颅面和躯干嵴衍生物的发展。我们集中我们的分析tfap 2a NA分化在中枢神经系统中的作用。在蓝斑中，Phox 2a和Tfap 2a共表达，并且都是NA发育所需的。相比之下，在髓质中，Phox 2a和Tfap 2a在相邻的重叠结构域中表达，但NA分化仅需要tfap 2a活性，因为NA神经元在无灵魂/phox 2a突变体髓质中正常发育。phox 2a和tfap 2a似乎不影响彼此的表达。我们的研究表明，两种不同的诱导机制控制NA的发展在斑马鱼后脑。对于后后脑，我们确定视黄酸作为一个重要的信号，以诱导NA分化的延髓和最后区，在那里它扩大了tfap 2a的表达结构域，从而作用于上游的tfap 2a。相比之下，以前的工作表明Fgf 8参与蓝斑NA神经元的规范。因此，虽然诱导信号可能是不同的，后脑NA神经元的蓝斑和后组都需要Tfap 2a，以建立其去甲肾上腺素能的身份。
Tfap2a is a transcriptional activator expressed in many different cell types, including neurons, neural crest derivatives and epidermis. We show that mutations at the zebrafish locus previously called mont blanc (mob) or lockjaw (low) encode tfap2a. The mutant phenotype reveals that tfap2a is essential for the development of hindbrain noradrenergic (NA) neurons of the locus coeruleus, medulla and area postrema, as well as for sympathetic NA neurons, epibranchial placode derived visceral sensory ganglia, and craniofacial and trunk crest derivatives. We focus our analysis on the role of tfap2a NA differentiation in the CNS. In the locus coeruleus, Phox2a and Tfap2a are co-expressed and are both required for NA development. By contrast, in the medulla Phox2a and Tfap2a are expressed in adjacent overlapping domains, but only tfap2a activity is required for NA differentiation, as NA neurons develop normally in soulless/phox2a mutant medulla. phox2a and tfap2a do not appear to affect each others expression. Our studies show that two distinct inductive mechanisms control NA development in the zebrafish hindbrain. For the posterior hindbrain, we identify retinoic acid as an important signal to induce NA differentiation in the medulla oblongata and area postrema, where it expands the tfap2a expression domain and thus acts upstream of tfap2a. By contrast, previous work revealed Fgf8 to be involved in specification of NA neurons in the locus coeruleus. Thus, although the inductive signals may be distinct, hindbrain NA neurons of the locus coeruleus and the posterior groups both require Tfap2a to establish their noradrenergic identity.