Document Type

Article

Publication Date

10-30-2017

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This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.

It is the author’s final published version in Frontiers in Cell and Developmental Biology

Volume 5, Issue OCT, October 2017, Article number 94.

The published version is available at DOI: 10.3389/fcell.2017.00094. Copyright © Suttorp et al.

Abstract

Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO), which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO) mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling. © 2017 Suttorp, Cremers, van Rheden, Regan, Helmich, van Kempen, Kuijpers-Jagtman and Wagener.

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