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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Molecular and Cellular Pathology

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1569533

This article is part of the Research Topic Molecular Basis of Craniofacial Abnormalities View all 6 articles

p75 Neurotrophin Receptor Regulates Craniofacial Growth and Morphology in Postnatal Development

Provisionally accepted
Byron Zhao Byron Zhao 1Jinsook Suh Jinsook Suh 1Yan Zhang Yan Zhang 1Eric Yin Eric Yin 1Chiho Kadota-Watanabe Chiho Kadota-Watanabe 1In Won Chang In Won Chang 2Jun Yaung Jun Yaung 2Isabelle Lao-Ngo Isabelle Lao-Ngo 1Nathan M. Young Nathan M. Young 1Reuben Han-Kyu Kim Reuben Han-Kyu Kim 2Ophir D Klein Ophir D Klein 1,3Christine Hong Christine Hong 1*
  • 1 University of California, San Francisco, San Francisco, United States
  • 2 University of California, Los Angeles, California, United States
  • 3 Cedars Sinai Medical Center, Los Angeles, California, United States

The final, formatted version of the article will be published soon.

    Craniofacial abnormalities are among the most prevalent congenital defects, significantly affecting appearance, function, and quality of life. While the role of genetic mutations in craniofacial malformations is recognized, the underlying molecular mechanisms remain poorly understood. In this study, we investigate the role of p75 neurotrophin receptor (p75 NTR ) in craniofacial development by comparing wild-type (p75 NTR+/+ ) mice against p75 NTR -deficient (p75 NTR-/-) knockout mice. We employed histology, micro-CT surface distance, volumetric analysis, and geometric morphometric analysis to assess craniofacial development and growth. On postnatal day 7 (P7), p75 NTR-/-mice exhibited reduced skull length compared to wild-type controls. By P28, micro-CT analysis revealed significant reductions in calvarial bone volume and trabecular bone thickness in p75 NTR-/-mice. Geometric morphometric analysis identified significant shape alterations in the nasal, parietal, and occipital regions, with p75 NTR-/-mice showing a shortened cranium and tapered nasal bone morphology. These findings highlight the critical role of p75 NTR in regulating postnatal craniofacial development. Disruption of p75 NTR signaling impairs both the growth and morphological integrity of craniofacial structures, which may contribute to the pathogenesis of congenital craniofacial abnormalities. In the future, a better understanding of the molecular mechanisms through which p75 NTR mediates craniofacial development may offer valuable insights for future targeted therapeutic strategies for craniofacial defects.

    Keywords: P75 NTR, CD271, NGF, Craniofacial Development, craniofacial morphogenesis, Calvarial development, Geometric morphometric analysis

    Received: 01 Feb 2025; Accepted: 03 Mar 2025.

    Copyright: © 2025 Zhao, Suh, Zhang, Yin, Kadota-Watanabe, Chang, Yaung, Lao-Ngo, Young, Kim, Klein and Hong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Christine Hong, University of California, San Francisco, San Francisco, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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