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Developmental Changes in Postnatal Murine Intestinal Interstitial Cell of Cajal Network Structure and Function

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Abstract

The mammalian gastrointestinal (GI) tract undergoes rapid development during early postnatal life in order to transition from a milk to solid diet. Interstitial cells of Cajal (ICC) are the pacemaker cells that coordinate smooth muscle contractility within the GI tract, and hence we hypothesized that ICC networks undergo significant developmental changes during this early postnatal period. Numerical metrics for quantifying ICC network structural properties were applied on confocal ICC network imaging data obtained from the murine small intestine at various postnatal ages spanning birth to weaning. These imaging data were also coupled to a biophysically-based computational model to simulate pacemaker activity in the networks, to quantify how changes in structure may alter function. The results showed a pruning-like mechanism which occurs during postnatal development, and the temporal course of this phenomenon was defined. There was an initial ICC process overgrowth to optimize network efficiency and increase functional output volume. This was followed by a selective retaining and strengthening of processes, while others were discarded to further elevate functional output volume. Subsequently, new ICC processes were formed and the network was adjusted to its adult morphology. These postnatal ICC network developmental events may be critical in facilitating mature digestive function.

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Abbreviations

CNS:

Central nervous system

DMP:

Deep muscular plexus

ENS:

Enteric nervous system

GI:

Gastrointestinal

ICC:

Interstitial cells of Cajal

MP:

Myenteric plexus

SMC:

Smooth muscle cell(s)

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Acknowledgments

The authors would like to thank Dr. Feng Mei for beneficial discussion and critical review of the paper, and Dr. Niranchan Paskaranandavadivel for assessing the quality of the ICC imaging data. The authors also wish to acknowledge the contribution of the NeSI high-performance computing facilities at the University of Auckland and the staff at NeSI and Centre for eResearch. J.G. is supported by a University of Auckland Health Research Doctoral Scholarship, a Freemasons Postgraduate Scholarship, and a R. H. T. Bates Postgraduate Scholarship. This work is funded in part by grants from the Riddet Institute, New Zealand Health Research Council, and National Institutes of Health (R01 DK64775).

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Authors and Affiliations

  1. Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Jerry Gao, Shameer Sathar, Gregory O’Grady & Leo K. Cheng

  2. Department of Surgery, University of Auckland, Auckland, New Zealand

    Gregory O’Grady

  3. Emergency Department, PLA 324 Hospital, Chongqing, 400020, China

    Juan Han

  4. Department of Surgery, Vanderbilt University, Nashville, TN, 37240, USA

    Leo K. Cheng

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  1. Jerry Gao
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  2. Shameer Sathar
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  5. Leo K. Cheng
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Correspondence to Leo K. Cheng.

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Associate Editor Dan Elson oversaw the review of this article.

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Gao, J., Sathar, S., O’Grady, G. et al. Developmental Changes in Postnatal Murine Intestinal Interstitial Cell of Cajal Network Structure and Function. Ann Biomed Eng 42, 1729–1739 (2014). https://doi.org/10.1007/s10439-014-1021-9

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  • DOI: https://doi.org/10.1007/s10439-014-1021-9

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