Lillesaar Christina, Tannhäuser Birgit, Stigloher Christian, Kremmer Elisabeth, Bally-Cuif Laure
Zebrafish Neurogenetics Junior Research Group, Institute of Virology, Technical University-Munich, Munich, Germany.
Dev Dyn. 2007 Apr;236(4):1072-84. doi: 10.1002/dvdy.21095.
To gain knowledge about the developmental origin of serotonergic precursors and the regulatory cascades of serotonergic differentiation in vertebrates, we determined the spatiotemporal expression profile of the Ets-domain transcription factor-encoding gene pet1 in developing and adult zebrafish. We show that it is an early, specific marker of raphe serotonergic neurons, but not of other serotonergic populations. We then use pet1 expression together with tracing techniques to demonstrate that serotonergic neurons of rhombomeres (r) 1-2 largely originate from a progenitor pool at the midbrain-hindbrain boundary. Furthermore, by combining expression analyses of pet1 and the raphe tryptophan hydroxylase (Tph2) with rhombomere identity markers, we show that anterior and posterior hindbrain clusters of serotonergic precursors are separated by r3, rather than r4 as in other vertebrates. Our findings establish the origin of r1-2 serotonergic precursors, and strengthen the evidence for molecular, ontogenic and phylogenic heterogeneities among the vertebrate brain serotonergic cell populations.
为了了解脊椎动物中血清素能前体的发育起源以及血清素能分化的调控级联反应，我们确定了Ets结构域转录因子编码基因pet1在发育中和成年斑马鱼中的时空表达谱。我们发现它是中缝血清素能神经元的早期特异性标志物，但不是其他血清素能群体的标志物。然后，我们利用pet1表达和追踪技术来证明，菱脑节（r）1-2的血清素能神经元主要起源于中脑-后脑边界处的一个祖细胞池。此外，通过将pet1和中缝色氨酸羟化酶（Tph2）的表达分析与菱脑节身份标志物相结合，我们发现血清素能前体的后脑前后簇被r3分隔，而不像其他脊椎动物那样被r4分隔。我们的研究结果确定了r1-2血清素能前体的起源，并加强了脊椎动物脑血清素能细胞群体之间分子、个体发生和系统发育异质性的证据。
