Details

Autor(en) / Beteiligte

• Hallikas, Outi
• Das Roy, Rishi
• Christensen, Mona M.
• Renvoisé, Elodie
• Sulic, Ana‐Marija
• Jernvall, Jukka

Titel

System‐level analyses of keystone genes required for mammalian tooth development

Ist Teil von

• Journal of experimental zoology. Part B, Molecular and developmental evolution, 2021-01, Vol.336 (1), p.7-17

Ort / Verlag

United States: John Wiley and Sons Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• When a null mutation of a gene causes a complete developmental arrest, the gene is typically considered essential for life. Yet, in most cases, null mutations have more subtle effects on the phenotype. Here we used the phenotypic severity of mutations as a tool to examine system‐level dynamics of gene expression. We classify genes required for the normal development of the mouse molar into different categories that range from essential to subtle modification of the phenotype. Collectively, we call these the developmental keystone genes. Transcriptome profiling using microarray and RNAseq analyses of patterning stage mouse molars show highly elevated expression levels for genes essential for the progression of tooth development, a result reminiscent of essential genes in single‐cell organisms. Elevated expression levels of progression genes were also detected in developing rat molars, suggesting evolutionary conservation of this system‐level dynamics. Single‐cell RNAseq analyses of developing mouse molars reveal that even though the size of the expression domain, measured in the number of cells, is the main driver of organ‐level expression, progression genes show high cell‐level transcript abundances. Progression genes are also upregulated within their pathways, which themselves are highly expressed. In contrast, a high proportion of the genes required for normal tooth patterning are secreted ligands that are expressed in fewer cells than their receptors and intracellular components. Overall, even though expression patterns of individual genes can be highly different, conserved system‐level principles of gene expression can be detected using phenotypically defined gene categories. A classification scheme is constructed for genes required for the development of mouse molar teeth, followed by gene expression analyses of the classifications. Research Highlights The phenotypic severity of mutations on mouse teeth is used to classify genes. Genes essential for the progression of odontogenesis are highly expressed at the organ and cell level. Many of the genes required for normal patterning are locally expressed ligands.