Details

Autor(en) / Beteiligte

• Book, Shae A.
• Moore, Alyssa C.
• Tourigny, Madeline S. G.
• Barr, Kevin
• Willmore, Katherine E.

Titel

Discordant growth of nasal cartilage and bone contributes to phenotypic variability of the skull in a mouse model

Ist Teil von

• Developmental dynamics, 2023-07, Vol.252 (7), p.1009-1025

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Background We previously determined a nonlinear relationship between connexin 43 (Cx43) function and craniofacial phenotypic variation in the mutant mouse model G60S/+, and that this variation was driven by nasal bone deviation. While nonlinearities in the genotype‐phenotype map appear to be common, few studies have looked at the developmental processes that underlie this nonlinearity. Here, we investigated the potential tissue‐level developmental determinants of the variation in nasal bone phenotype in G60S/+ mice through postnatal development. Results The deviated nasal bone phenotype arises by postnatal day 21 and becomes more severe by 3 months in G60S/+ mice. Measures of nasal bone remodeling including the number of osteoclasts, mineralizing surface, mineral apposition rate, and bone formation rate are significantly greater in G60S/+ mice compared to wild‐type mice at 2 months, but these differences do not correspond with nasal bone deviation. The degree of nasal bone deviation does significantly and negatively correlate with the ratio between nasal bone and cartilaginous nasal septum length. Conclusions Our findings indicate that the mean phenotypic changes observed between G60S/+ and wild‐type mice are due to reduced bone growth, but the increased phenotypic variation found within mutant mice is due to discordant growth between nasal cartilage and bone. Key Findings Mean nasal bone differences between G60S/+ mutant and wildtype mice are due in part to reduced bone growth. Phenotypic variation observed in G60S/+ nasal bones is due in part to uncoupling of nasal cartilage and bone growth. Separate tissue-level processes underlie differences in mean shape and shape variation of nasal bones in G60S/+ mutant mice.