Jiang Lab

  • Molecular Patterning of Mammalian Organogenetic Fields

    Development of all organs involves precisely controlled cell-cell interactions that are regulated by specific transcription factors and intercellular signaling pathways. We found that the odd-skipped family transcription factors Osr1 and Osr2 play critical roles in patterning organogenetic fields in mice.

    Osr1 is expressed throughout the intermediate mesoderm during early mouse embryogenesis, and its expression domain is gradually restricted to nephrogenic mesenchyme of the developing metanephric kidney. We generated Osr1 knockout mice and found that these mutant mice failed to initiate metanephric kidney development. In addition, Osr1 mutant mice had defects in other intermediate mesoderm derived organs, including adrenal glands, mesonephros and gonads. We have recently generated Osr1 conditional mutant mice and will carry out detailed dissection of Osr1 function and molecular pathways in organogenesis and progenitor cell maintenance in the intermediate mesoderm.

    Osr2, on the other hand, exhibits a unique gradient expression pattern surrounding the developing molar tooth germs. Through detailed phenotypic and molecular genetic analyses, we found that Osr2 plays a critical role in restricting tooth development in a single row. Recently, we found that Osr2 interacts with multiple transcription factors, including Msx1, Pax9 and Runx2, involved in the regulation of tooth inductive signals. We are using laser capture microdissection of specific regions of the developing tooth germs and microarray / RNAseq approaches in combination with compound mutant mouse studies to characterize the roles and interactions of these transcription factors in patterning the tooth developmental field.

    Together, these studies of intermediate mesoderm organogenesis and tooth development will lead to significant advances in understanding of the molecular mechanisms of mammalian organogenesis and will help develop new strategies for tissue / organ regeneration.

 
  • molecular-visual1-450

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    molecular-visual1-450
    Osr1 is expressed in the developing intermediate mesoderm and required for kidney organogenesis. (A, B) Whole mount X-gal staining showing Osr1-LacZ expression in the early intermediate mesoderm of E7.5 (A) and E8.5 (B) Osr1lacZ/+heterozygous mouse embryos. (C-F) Osr1-/- mutant mouse embryos (D and F) exhibit complete failure of initiation of metanephric kidney organogenesis as well as defects in the mesonephros and nephric duct, in comparison with the control littermates (C and E, respectively). Arrows point to the nephric duct. Gr = genital ridge. Ki = kidney. Li = liver.  Mn = mesonephros. Pm = primitive streak. S = somite. St = stomach.
  • patterning-visual2-450

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    patterning-visual2-450
    Osr2 patterns the tooth developmental field. (A, B) Frontal sections of control (A) and Osr2-/- mutant (B) mice showing development of supernumerary tooth germs (arrows) lingual to the first molar (m1) in both the maxilla and mandible in the mutant. (C-F) Development of the supernumerary teeth in Osr2-/- mutant mice begins with ectopic thickening of the oral epithelium separate from the first molar tooth bud (D), followed by invagination of the epithelium into the underlying mesenchyme to form an ectopic bud (E) and then cap (F) stage of tooth morphogenesis.