Embryological Origins of Developmental Stability: Size, Shape and Fluctuating Asymmetry in Prenatal Random Bred Mice BENEDIKT HALLGRI ´ MSSON, n1 TSUTOMO MIYAKE, 2 KATHERINE WILMORE, 1 and BRIAN K. HALL 3 1 Department of Cell Biology & Anatomy, University of Calgary, Calgary, Alberta, T2N 4N1, Canada 2 Virginia Mason Research Center, Seattle, Washington 98101-2795 3 Department of Biology, Dalhousie University, Halifax, Nova Scotia, B3H 4J1, Canada ABSTRACT Ontogenetic patterns of fluctuating asymmetry (FA) can be used to test models for the mechanisms underlying stability during embryonic development (developmental stability). In this study, we ask whether developmental processes initially show high levels of instability that are subsequently dampened through active compensatory mechanisms or passive properties of developmental systems or whether the effects of instability accumulate during embryonic development causing random drift away from an earlier stable state. Previous work on this question has dealt with postnatal skeletal growth and thus been unable to effectively distinguish developmental instability from the effects of mechanically mediated variation in bone modeling and remodeling. Here, we report that FA variances of limb skeletal elements in CD1 mice decrease with gestational age from day 14 to birth (day 20.5). Thus, in mouse limbs, skeletal development is characterized by a high level of developmental instability initially that is reduced during subsequent prenatal development. These results are consistent with the existence of active mechanisms that compensate for the effects of minor perturbations or deviations during development. However, they are also consistent with Soule’s model of allomeric variation in which the variance of structures is reduced as the number of independent developmental events that produce them increases. This study illustrates that predictions based on morphometric analyses can yield insights into general properties of developmental systems in cases where specific developmental mechanisms are not yet known. J. Exp. Zool. (Mol. Dev. Evol.) 296B:40–57, 2003. r 2003 Wiley-Liss, Inc. Despite recent interest, the developmental mechanisms that underlie developmental instabil- ity and its variation remain poorly understood. Complementary approaches to this problem have emerged, ranging from quantitative trait locus mapping (Leamy et al., ’97, ’98) and studies of the effects of specific mutations on developmental instability (Atchley et al., ’84; Clarke and McKen- zie, ’87; McKenzie and Clarke, ’88) to studies that relate mechanistic models to predictions at the morphological level (Aparicio, 2001; Hallgrı ´msson, ’98, ’99; Klingenberg and Nijhout, ’99; Klingen- berg, 2002). The third type of study represents a less direct approach to the problem compared with the other two. Studies of patterns of morphological variability are valuable because they allow ques- tions to be posed at a more general mechanistic level. If carefully constructed, the results of such studies can be valuable guides for the formulation of studies that target specific developmental- genetic mechanisms. Fluctuating asymmetry (FA) refers to the variance of deviations from symmetry that is normally distributed in magni- tude and random with respect to side. In struc- tures in which the developmental-genetic program does not differ between the sides, such deviations are thought to represent the effects of random Grant sponsor: NSERC; Grant number: 238992-02 (to BH); Grant number: A5051 (to BKH); Grant sponsor: RCMI; Grant number: RR 03051; Grant sponsors: CIDIC (UPR, School of Medicine), University of Calgary (to BH). n Correspondence to: Benedikt Hallgrı ´msson, Dept. of Cell Biology & Anatomy, University of Calgary, 3330 Hospital Dr., Calgary, AB T2N 4N1, Canada. E-mail: bhallgri@ucalgary.ca Received 15 August 2002; Accepted 18 November 2002 Published online in Wiley InterScience (www.interscience.wiley. com). DOI: 10.1002/jez.b.00015 r 2003 WILEY-LISS, INC. JOURNAL OF EXPERIMENTAL ZOOLOGY (MOL DEV EVOL) 296B:40–57 (2003)