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Shiroishi, T.

Publications and source records attributed to Shiroishi, T..

2 recordsLinked to original sources

High-Resolution Maps of Mouse Reference Populations

Genetic reference panels are widely used to map complex, quantitative traits in model organisms. We have generated new high-resolution genetic maps of 259 mouse inbred strains from recombinant inbred strain panels (C57BL/6J x DBA/2J, ILS/IbgTejJ x ISS/IbgTejJ, C57BL/6J x A/J) and chromosome substitution strain panels (C57BL/6J-Chr# , C57BL/6J-Chr# , C57BL/6JChr# ). We genotyped all samples using the Affymetrix Mouse Diversity Array with an average inter-marker spacing of 4.3kb. The new genetic maps provide increased precision in the localization of recombination breakpoints compared to the previous maps. Although the strains were presumed to be fully inbred, we found residual heterozygosity in 40% of individual mice from five of the six panels. We also identified de novo deletions and duplications, in homozygous or heterozygous state, ranging in size from 21kb to 8.4Mb. Almost two-thirds (46 out of 76) of these deletions overlap exons of protein coding genes and may have phenotypic consequences. Twenty-nine putative gene conversions were identified in the chromosome substitution strains. We find that gene conversions are more likely to occur in regions where the homologous chromosomes are more similar. The raw genotyping data and genetic maps of these strain panels are available at http://churchill-lab.jax.org/website/MDA.

genetics

Sonic hedgehog is required for neural crest-dependent patterning of the intrinsic tongue musculature

The tongue is a highly specialized muscular organ important for breathing, speech, taste and swallowing. The secreted signaling molecule Sonic hedgehog (Shh) is expressed in dorsal tongue epithelium from the initial developmental stage. In this study, we utilized a series of genetic approaches to investigate the role of Shh during mouse tongue formation. Temporal-specific global deletion of Shh demonstrated a functional requirement for normal patterning of the intrinsic tongue muscles and establishment of the lingual tendon. These defects were reproduced in the mutant with a specific loss of signaling in oropharyngeal epithelium by a Shh cis-enhancer. In these mutants, Ptch1 was lost in the underlying cranial neural crest (CNC)-derived mesenchymal lineage. The importance of Shh was confirmed by generating tissue-specific deletions in the ciliopathy gene Ofd1, which transduces Shh signaling. These results revealed Shh roles in patterning of the mesodermal intrinsic tongue muscles through CNC-derived mesenchyme, including the lingual tendon.

developmental biology