Building a second brain in the bowel
Marina Avetisyan, … , Ellen Merrick Schill, Robert O. Heuckeroth
Marina Avetisyan, … , Ellen Merrick Schill, Robert O. Heuckeroth
Published February 9, 2015
Citation Information: J Clin Invest. 2015;125(3):899-907. https://doi.org/10.1172/JCI76307.
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Building a second brain in the bowel

Abstract

The enteric nervous system (ENS) is sometimes called the “second brain” because of the diversity of neuronal cell types and complex, integrated circuits that permit the ENS to autonomously regulate many processes in the bowel. Mechanisms supporting ENS development are intricate, with numerous proteins, small molecules, and nutrients that affect ENS morphogenesis and mature function. Damage to the ENS or developmental defects cause vomiting, abdominal pain, constipation, growth failure, and early death. Here, we review molecular mechanisms and cellular processes that govern ENS development, identify areas in which more investigation is needed, and discuss the clinical implications of new basic research.

Authors

Marina Avetisyan, Ellen Merrick Schill, Robert O. Heuckeroth

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Figure 1

ENS morphogenesis.

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ENS morphogenesis. (A) Vagal ENCDCs migrate in a rostral to caudal direc...
(A) Vagal ENCDCs migrate in a rostral to caudal direction through fetal bowel (long white arrow). At E12.5 ENS precursors have migrated halfway through the fetal colon. ANNA-1 antibody binds HuC/D antigen and identifies enteric neurons (magenta), while TuJ1 binds neuron-specific β-III tubulin and labels neurites (green). ENCDCs migrate in chains though the bowel, but during the period of migration some precursors differentiate into neurons and extend neurites, including at the migration wavefront (white arrows). (B) Adult small bowel myenteric plexus, indicated by ANNA-1 antibody (red, neurons), SOX10 antibody (green, enteric glia), and TuJ1 antibody (blue), demonstrates clusters of neurons and glia in mature ganglia as well as many neurites within and between ganglia. Scale bars: 100 microns.