Sonic hedgehog expression in the postnatal brain
Sonic hedgehog expression in the postnatal brain
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DOI：
10.1242/bio.040592
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发表时间：
2019-03-01
期刊：
影响因子：
2.4
通讯作者：
Yao, Pamela J.
中科院分区：
文献类型：
--
作者：
Rivell, Aileen;Petralia, Ronald S.;Yao, Pamela J.
除了在胚胎发生过程中形成神经管模式的作用之外，音速刺猬 (Shh) 在胚胎后和成熟大脑中的其他功能也已成为人们关注的焦点。然而，内源性Shh（信号通路的配体）的丰度及其在胚胎后和成熟大脑中随时间的变化的问题尚不清楚。在这里，我们发现，虽然大鼠大脑中的Shh转录物和蛋白质的量在出生时几乎检测不到，但它们在出生后发育过程中不断增加，并且在年轻人中保持在容易检测到的水平。这种与发育年龄相关的Shh水平的增加也出现在培养物中生长的海马神经元中，其中非常年轻的神经元产生极少量的Shh蛋白，但随着神经元生长并形成突触，Shh的量显着增加。使用针对Shh不同残基的抗体进行免疫标记，我们观察到Shh的N端片段和C端片段存在于海马神经元中，并且这两种Shh形式在神经元的大多数区室中共存。我们的研究结果提供了对大脑中Shh表达的更好理解，为进一步理解年轻和成熟大脑和神经元中Shh蛋白的生物发生奠定了基础。
Beyond its role in patterning the neural tube during embryogenesis, additional functions of Sonic hedgehog (Shh) in post-embryonic and mature brains have been coming into focus. However, the question of the abundance of endogenous Shh - the ligand of the signaling pathway - and its changes over time in post-embryonic and mature brains are less well understood. Here we find that while the amounts of Shh transcript and protein in rat brains are nearly undetectable at birth, they increase continuously during postnatal development and remain at readily detectable levels in young adults. This developmental age-associated increase in Shh levels is also seen in hippocampal neurons grown in culture, in which very young neurons produce minimal amounts of Shh protein but, as neurons grow and form synapses, the amounts of Shh increase significantly. Using immunolabeling with antibodies to different residues of Shh, we observed that the N-terminal fragment and the C-terminal fragment of Shh are present in hippocampal neurons, and that these two Shh forms co-exist in most compartments of the neuron. Our findings provide a better understanding of Shh expression in the brain, laying the groundwork for further comprehending the biogenesis of Shh protein in the young and mature brain and neurons.