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RESEARCH REPORT
Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis
Melissa A. Pickett, Michael K. Dush, Nanette M. Nascone-Yoder
Development 2017 : dev.149831 doi: 10.1242/dev.149831 Published 6 July 2017
Melissa A. Pickett
Department of Biology, Environmental and Molecular Toxicology Program, North Carolina State University, Raleigh, NC, 27606, USA
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Michael K. Dush
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA
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Nanette M. Nascone-Yoder
Department of Biology, Environmental and Molecular Toxicology Program, North Carolina State University, Raleigh, NC, 27606, USADepartment of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA
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Abstract

Acetylcholinesterase (AChE) is crucial for degrading acetylcholine at cholinergic synapses. In vitro studies suggest that, in addition to its role in nervous signaling, AChE can also modulate non-neuronal cell properties, although it remains controversial whether AChE functions in this capacity in vivo. Here, we show that AChE plays an essential non-classical role in vertebrate gut morphogenesis. Exposure of Xenopus embryos to AChE-inhibiting chemicals results in severe defects in intestinal development. Tissue-targeted loss of function assays (via microinjection of antisense morpholino or CRISPR-Cas9) confirm that AChE is specifically required in the gut endoderm tissue, a non-neuronal cell population, where it mediates adhesion to fibronectin and regulates cell rearrangement events that drive gut lengthening and digestive epithelial morphogenesis. Notably, the classical esterase activity of AChE is dispensable for this activity. As AChE is deeply conserved, widely expressed outside of the nervous system, and the target of many environmental chemicals, these results have broad-reaching implications for development and toxicology.

  • Received January 27, 2017.
  • Accepted June 19, 2017.
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Keywords

  • Acetylcholinesterase
  • Morphogenesis
  • Gut
  • Intestine
  • Fibronectin
  • Xenopus

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Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis
Melissa A. Pickett, Michael K. Dush, Nanette M. Nascone-Yoder
Development 2017 : dev.149831 doi: 10.1242/dev.149831 Published 6 July 2017
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Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis
Melissa A. Pickett, Michael K. Dush, Nanette M. Nascone-Yoder
Development 2017 : dev.149831 doi: 10.1242/dev.149831 Published 6 July 2017

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