Meeting Abstract

144.3  Monday, Jan. 7  Developmental influences on variation and asymmetry of the jaw. FISH, JL*; DEPEW, MJ; MARCUCIO, RS; Univ. of California, San Francisco; Univ. of California, San Francisco; Univ. of California, San Francisco jennifer.fish@ucsf.edu

Evo-devo as a discipline seeks to understand how variation is generated in a way that can influence evolution. Variation is a salient feature of both normal and abnormal development, but the mechanisms responsible for its generation are largely unknown. We investigate developmental mechanisms generating variation in the lower jaw, or mandible, utilizing two strains of mutant mice that exhibit variable reduction in jaw size and asymmetry, Fgf8 and Satb2. Fgf8 is a secreted signaling factor that is expressed in multiple domains of the epithelia surrounding the developing jaw. Satb2 is a transcription factor that is expressed in the mesenchyme of the developing jaw. Reduction in gene dosage of either Fgf8 or Satb2 causes micrognathia. Although both mutants exhibit asymmetry in the severity of the defects, Fgf8 mutants exhibit directional asymmetry, with the left side of the jaw more severely affected. In contrast, asymmetry in Satb2 heterozygotes is random. Further, significant reduction in jaw length is observed in mice heterozygous for Satb2 (~50% Satb2), whereas mice heterozygous for Fgf8^Delta (~50% Fgf8) alleles are phenotypically normal. Micrognathia occurs in Fgf8 mutants only when Fgf8 is less than 40% (Fgf8^Neo/Neo mutants). Notably, Satb2^+/- (heterozygous) mice have greater variation in mandibular length relative to both WT and mutant genotypes. These data indicate a non-linear relationship between genotype and phenotype, which likely derives from random perturbations in other intrinsic factors. We discuss how differences in the regulation of Fgf8 and Satb2 may contribute to differences in their susceptibility to random developmental perturbations, and thus differences in variation in RNA and protein levels and, ultimately, jaw size.