Browsing by Author "Schmidt, Eric J"
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- ItemOpen AccessFunctional basis of cleft lip liability in a-strain mice(2012) Schmidt, Eric J; Hallgrimsson, Benedikt; Jirik, FrankThe "facial shape hypothesis" holds that cleft lip penetrance rates among A-strain lines differ owing to subtle genetic differences in midfacial primordia size, orientation, and rates of growth-summarily "facial shape"-that place more liable lines closer to, and less liable Jines further from, a threshold shape value that is set by physical constraints limiting the range of shape variation tolerated before the primordia fail to contact or consolidate adequately into a unified structure separating the nasal slits from the mouth. Fixation for an IAP allele of Wnt9b, which plays a regulatory role in midfacial development, is a key component of the genetic liability. Variation in genetic maternal effects modifies penetrance rates through an unknown function. I tested the hypothesis that maternal background influences the rate clefted primary palates in litters by differentially shifting the distributions of Wnt9b IAP epigenetic modification toward an expression threshold set by a common level of tolerance for low Wnt9b expression in the developing upper jaw. IAP methylation profiles between a reciprocal pair of hybrids with a two-fold difference in liability did not substantially differ. Nor did a morphometric analysis suggest that genetic maternal effects differences influenced embryonic facial shape. The data imply a role for maternal effects variation impacting palatogenesis via a mechanism outside epigenetic modification of the Wnt9b IAP but also independent of normal variations in midfacial shape with respect to a shape threshold. The significance of the alternative "two state" hypothesis, holding that penetrance rate differences among the A-strain are a function of the rate at which somatic differences arise between normal and cleft penetrant embryos, is considered.