TY - JOUR T1 - Keystone genes of mammalian tooth patterning and quantification of their expression JF - bioRxiv DO - 10.1101/869065 SP - 869065 AU - Outi Hallikas AU - Rishi Das Roy AU - Mona M. Christensen AU - Elodie Renvoisé AU - Ana-Marija Sulic AU - Jukka Jernvall Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/12/15/869065.abstract N2 - Organ development is regulated by complex interactions of multiple regulatory pathways. These pathways (Wnt, Tgfβ, Fgf, Hh, Eda, Notch) are becoming increasingly better known, with many identified genes having well-characterized effects on the phenotype. We classify genes required for normal organogenesis into different categories that range from essential to subtle modification of the phenotype. We focus on the mouse tooth development in which over 70 genes are known to be required for normal odontogenesis. These genes were classified into progression, shape, and tissue categories based on whether their null mutations cause early developmental arrests, altered morphologies, or hard tissue defects, respectively. Collectively, we call these here the developmental keystone genes. Additionally, we identified 100 developmental genes with no phenotypic effects on molars when null mutated, thereby providing the means to contrast expression dynamics between keystone and non-keystone genes. Transcriptome profiling using microarray and RNAseq analyses of patterning stage mouse molars show elevated expression levels for progression and shape genes, the former category showing the most significant upregulation. Single-cell RNAseq analyses reveal that even though the size of the expression domain, measured in number of cells, is the main driver of organ-level expression, the progression genes show high cell-level transcript abundances. In contrast, high proportion of the shape genes are secreted ligands that are found to be expressed in fewer cells than their receptors and intracellular components. Overall, we postulate that genes essential for the progression of organ patterning are characterized by high level of expression, whereas fine-tuning of the pattern is more dependent on spatially restricted production of ligands. The combination of phenotypically defined gene categories and transcriptomes allow the characterization of the expression dynamics underlying different aspects of organogenesis. ER -