Postnatal Ontogeny of the Cranial Base and Craniofacial Skeleton in Male C57BL/6J Mice: A Reference Standard for Quantitative Analysis.

Siddharth R Vora,Timothy C Cox,Esra D Camci

doi:10.3389/fphys.2015.00417

Siddharth R Vora, Timothy C Cox + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2015.00417

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Abstract

Growth of the craniofacial skeleton is a complex process controlled by both genetic and epigenetic factors, perturbations of which can lead to varying degrees of dysmorphology. Mouse models that recapitulate clinical craniofacial phenotypes are instrumental in studying the morphogenetic progression of diseases as well as uncovering their genetic and molecular bases. Commonly encountered phenotypes in these models include defects in the cranial base synchondroses, calvarial sutures, mandible or the midface, or any combination thereof, with the concurrent presence of altered overall craniofacial growth. However, the literature lacks an adequate normative timeline of developmental events and growth trends that shape the mouse craniofacial skeleton. In this report, we analyzed the postnatal craniofacial ontogeny (from postnatal day 7 [P7] through to P112) of male mice from the most widely used inbred mouse strain, C57BL/6J, using high-resolution microcomputed tomography (μCT) in combination with classic morphometric approaches. We also evaluated cranial base synchondroses at the histological level, and compared it to μCT-generated data to assess the timing and pattern of closure of these structures. Our data underscore the complex and unique growth patterns of individual bones and cranial regions and highlight the need to include younger animals in studies aimed at analyzing craniofacial growth processes. Furthermore, these data serve as a reference standard for future quantitative work.

Highlights

One in four birth defects have craniofacial involvement, with many patients requiring significant orthodontic, orthopedic, or surgical intervention (Posnick and Ruiz, 2000; Cunningham et al, 2007; Saltaji et al, 2014)
Postnatal growth of the C57BL/6J craniofacial skeleton was quantified by measuring changes in length along the transverse, vertical, and antero-posterior (A-P) planes as well as angular changes in the mid-sagittal plane in animals at P7, P14, P21, P28, P56, P84, and P112
While most studies identify the cranial base, the cranial vault, and the face as morphologically semiindependent modules, it has been shown that the cranial vault and base behave developmentally as one integrated complex (Lieberman et al, 2000; Hallgrímsson et al, 2007)

Summary

Introduction

One in four birth defects have craniofacial involvement, with many patients requiring significant orthodontic, orthopedic, or surgical intervention (Posnick and Ruiz, 2000; Cunningham et al, 2007; Saltaji et al, 2014). Animal models have played a pivotal role in understanding the genetic mechanisms and pathways involved in some of these disease processes, through the investigation of mutant phenotypes in mice (Wilkie and Morriss-Kay, 2001; Hallgrímsson and Lieberman, 2008). Postnatal Cranioskeletal Ontogeny in C57BL/6J human disorders in laboratory mouse models (like the C57BL/6J) include their uniform genetic background, the relative ease with which their genome can be modified, and the degree to which their environment can be controlled. This level of experimental control allows investigators to dissect out the individual genetic and epigenetic contributions to phenotypes or disease states. The Jackson Laboratory (jax.org), the largest supplier of mouse resources for research, provides a set of basic cranioskeletal metrics for various wildtype and mutant strains based on caliper measurements, but more detailed data on the ontogeny of postnatal cranioskeletal growth is lacking

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