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Integrating central and peripheral neurons in elongating multi-lineage-organized gastruloids

View ORCID ProfileZachary T. Olmsted, Janet L. Paluh
doi: https://doi.org/10.1101/2020.12.29.424774
Zachary T. Olmsted
1State University of New York Polytechnic Institute, College of Nanoscale Science and Engineering, Nanobioscience Constellation, Albany, NY 12203
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  • ORCID record for Zachary T. Olmsted
Janet L. Paluh
1State University of New York Polytechnic Institute, College of Nanoscale Science and Engineering, Nanobioscience Constellation, Albany, NY 12203
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  • For correspondence: jpaluh@sunypoly.edu
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ABSTRACT

Human stem cell technologies including self-assembling 3D tissue models provide unprecedented access to early neurodevelopment and enable fundamental insights into neuropathologies. Gastruloid models have yet to be used to investigate the developing nervous system. Here we generate elongating multi-lineage-organized (EMLO) gastruloids with trunk identity that co-develop central and peripheral nervous system (CNS, PNS) correlates. We track migrating neural crest cells that differentiate to form peripheral neurons integrated with an upstream spinal cord region. This follows initial EMLO polarization events, and is coordinated with primitive gut tube elongation and cardiomyocyte differentiation. By immunofluorescence of multi-lineage and functional biomarkers, we evaluate EMLOs over a twenty-two day period, and apply them to investigate the impact of mu opioid receptor modulation on neuronal activity. This comprehensive study demonstrates a novel combined CNS-PNS model of early organogenesis and integration events in the trunk to benefit human biomedical research.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 30, 2020.
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Integrating central and peripheral neurons in elongating multi-lineage-organized gastruloids
Zachary T. Olmsted, Janet L. Paluh
bioRxiv 2020.12.29.424774; doi: https://doi.org/10.1101/2020.12.29.424774
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Integrating central and peripheral neurons in elongating multi-lineage-organized gastruloids
Zachary T. Olmsted, Janet L. Paluh
bioRxiv 2020.12.29.424774; doi: https://doi.org/10.1101/2020.12.29.424774

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