83 - Early Ontogenetic Appearance of a Negative Pleiotropy Effect in Mouse Zygomatic Arch Morphology

Poster Board Number: 83
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Abstract Body : A quantitative trait locus on chromosome 17 was previously associated with a negative correlation of adjacent bone lengths within the zygomatic arch region in a large heterogeneous adult mice population. For example, the effect of the NOD/ShiLtJ mouse strain haplotype led to a greater proportional contribution of the zygomatic process of the maxilla and a smaller contribution of the zygomatic bone to overall zygomatic arch length. The 129S1/SvlmJ strain haplotype had the opposite effect. This example of negative pleiotropy is an antagonistic genetic mechanism underlying variation in individual bone development while overall zygomatic arch length is conserved. Identifying the responsible allele within this chromosomal region and determining the impacted developmental mechanism will help us understand how overall skull integration is maintained in the face of genetic variation. The goal of the current study was to identify the earliest ontogenetic time point when this strain-specific effect on zygomatic arch morphology was present, as a first step towards determining the specific developmental processes that are modified to produce strain-specific skull morphology. We quantified the relative contributions of individual bones to overall zygomatic arch length from micro-Computed Tomography images of NOD and 129 mouse skulls at embryonic day 18.5 (E18.5), postnatal day 28 (P28) and 9-11 weeks (adult). We measured the lengths of the 1) zygomatic process of the maxilla, 2) zygomatic bone, and 3) zygomatic process of the temporal. Proportional contributions to the zygomatic arch were quantified as individual bone length divided by the sum of all bone lengths. Comparisons of relative lengths indicated broadly shared ontogenetic patterns, including a substantial increase in the contribution of the zygomatic bone to the zygomatic arch between E18.5 and P28 in both genotypes. Despite this shared pattern detected across genotypes, NOD mice display a relatively longer maxillary portion of the zygomatic arch and shorter zygomatic bone, in comparison to 129S1 mice at all three ages. This suggests that that the previously observed adult pattern of strain-specific zygomatic arch morphology has an embryonic origin earlier than E18.5. We hypothesize that relevant genetic variants on mouse chromosome 17 impact early skeletogenic processes as a foundation for the previously identified adult phenotype. However, contrary to expectations, adult strain differences in the contribution of the zygomatic process of the temporal is not detected at P28, suggesting a greater impact of postnatal growth and remodeling on how the temporal bone contributes to the zygomatic arch in adult mice. These results help to elucidate the developmental processes behind observed zygomatic variations and provide background for future efforts to understand the complex genetic and developmental interactions underlying the mouse strain-specific morphologies. Additionally, given that interspecies morphological differences in other skull components may be governed by similar negative pleiotropy effects, the current results should help elucidate general mechanisms that contribute to evolutionary variation and constraints across craniofacial morphology. This project was funded with Stony Brook University Startup funds to CJP.