Birthdating of myenteric neuron subtypes in the small intestine of the mouse.
Birthdating of myenteric neuron subtypes in the small intestine of the mouse.
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DOI：
10.1002/cne.23423
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发表时间：
2014-02-15
影响因子：
2.5
通讯作者：
Young, Heather M.
中科院分区：
文献类型：
--
作者：
Bergner, Annette J.;Stamp, Lincon A.;Gonsalvez, David G.;Allison, Margaret B.;Olson, David P.;Myers, Martin G., Jr.;Anderson, Colin R.;Young, Heather M.
有许多不同类型的肠神经细胞。以往的研究已经确定了一些肠神经元亚型在小鼠体内出生(退出细胞周期)的时间，但一些主要肠神经元亚型的出生日期仍不完全确定或未知。我们将5-乙炔-2‘-脱氧尿苷(EDU)标记与识别肌间神经元亚型的抗体标记相结合，以确定小鼠小肠中神经元亚型的出生时间。我们发现不同的神经化学类型的肠神经细胞的出生日期不同，5-羟色胺神经元最先出生，细胞周期高峰出现在E11.5，其次是神经丝-M神经元，降钙素基因相关肽神经元(细胞周期高峰出现在E12.5-E13.5)，酪氨酸羟基化酶神经元(E15.5)，一氧化氮合酶1(NOS1)神经元(E15.5)和钙视黄素神经元(P0)。到P10时，绝大多数肌间神经元已退出细胞周期。在E10.5或E11.5注射EDU后，我们没有在成年小鼠的小肠中观察到任何EDU+/NOS1+肌间神经元，这是意想不到的，因为先前的研究表明在E11.5小鼠中存在NOS1神经元。使用增殖标记Ki67的研究表明，E11.5和E12.5肠道中几乎没有NOS1神经元在增殖。然而，基于Cre-lox的遗传命运图谱显示，一小部分肌间神经元似乎只短暂地表达NOS1。总之，我们的结果证实了肠道神经元亚型与出生日期之间的关系，并表明一些肠道神经元在发育过程中表现出不同于其成熟表型的神经化学表型。
There are many different types of enteric neurons. Previous studies have identified the time at which some enteric neuron subtypes are born (exit the cell cycle) in the mouse, but the birthdates of some major enteric neuron subtypes are still incompletely characterized or unknown. We combined 5-ethynynl-2’-deoxyuridine (EdU) labeling with antibody markers that identify myenteric neuron subtypes to determine when neuron subtypes are born in the mouse small intestine. We found that different neurochemical classes of enteric neuron differed in their birthdates; serotonin neurons were born first with peak cell cycle exit at E11.5, followed by neurofilament-M neurons, calcitonin gene-related peptide neurons (peak cell cycle exit for both at E12.5-E13.5), tyrosine hydroxylase neurons (E15.5), nitric oxide synthase 1 (NOS1) neurons (E15.5) and calretinin neurons (P0). The vast majority of myenteric neurons had exited the cell cycle by P10. We did not observe any EdU+/NOS1+ myenteric neurons in the small intestine of adult mice following EdU injection at E10.5 or E11.5, which was unexpected as previous studies have shown that NOS1 neurons are present in E11.5 mice. Studies using the proliferation marker, Ki67, revealed that very few NOS1 neurons in the E11.5 and E12.5 gut were proliferating. However, Cre-lox-based genetic fate-mapping revealed a small sub-population of myenteric neurons that appears to express NOS1 only transiently. Together, our results confirm a relationship between enteric neuron subtype and birthdate, and suggest that some enteric neurons exhibit neurochemical phenotypes during development that are different from their mature phenotype.
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