Airway branching has conserved needs for local parasympathetic innervation but not neurotransmission.

Airway branching has conserved needs for local parasympathetic innervation but not neurotransmission.
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DOI:
10.1186/s12915-014-0092-2
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发表时间:
2014-11-11
期刊:
影响因子:
5.4
通讯作者:
Jesudason EC
Jesudason EC
中科院分区:
生物学2区
文献类型:
--
作者:
Bower DV;Lee HK;Lansford R;Zinn K;Warburton D;Fraser SE;Jesudason EC

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Parasympathetic signaling has been inferred to regulate epithelial branching as well as organ regeneration and tumor development. However, the relative contribution of local nerve contact versus secreted signals remains unclear. Here, we show a conserved (vertebrates to invertebrates) requirement for intact local nerves in airway branching, persisting even when cholinergic neurotransmission is blocked. In the vertebrate lung, deleting enhanced green fluorescent protein (eGFP)-labeled intrinsic neurons using a two-photon laser leaves adjacent cells intact, but abolishes branching. Branching is unaffected by similar laser power delivered to the immediately adjacent non-neural mesodermal tissue, by blocking cholinergic receptors or by blocking synaptic transmission with botulinum toxin A. Because adjacent vasculature and epithelial proliferation also contribute to branching in the vertebrate lung, the direct dependence on nerves for airway branching was tested by deleting neurons in Drosophila embryos. A specific deletion of neurons in the Drosophila embryo by driving cell-autonomous RicinA under the pan-neuronal elav enhancer perturbed Drosophila airway development. This system confirmed that even in the absence of a vasculature or epithelial proliferation, airway branching is still disrupted by neural lesioning. Together, this shows that airway morphogenesis requires local innervation in vertebrates and invertebrates, yet neurotransmission is dispensable. The need for innervation persists in the fly, wherein adjacent vasculature and epithelial proliferation are absent. Our novel, targeted laser ablation technique permitted the local function of parasympathetic innervation to be distinguished from neurotransmission. The online version of this article (doi:10.1186/s12915-014-0092-2) contains supplementary material, which is available to authorized users.
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