Pluto Bioinformatics

GSE76316: Transcriptomic signatures uncover gene expression differences associated with the development of phenotypic differences in serial organs

Bulk RNA sequencing

Gene expression differences during development provide the basis for adult phenotypic differences. This is true between species, but also between organs of the same type, yet with different shapes, within the same organism. In such serial organs, current models state that organ identity is initially provided by a few specifically expressed genes (e.g. homeotic genes) that initiate differential regulation in an otherwise common developmental program. We know surprisingly little about the nature and structure of expression differences later during organ morphogenesis in relation to organ identity. Better understanding this would provide insights to how differences in gene expression during development ultimately result in organs that are similar, yet different. To address this question, we focused on the morphogenesis of two well-differentiated serial appendages, the upper and lower first molars in mouse. We analyzed tight RNA-seq transcriptome timeseries taken in their entirety with a set of purposely developed bioinformatic tools and complementary bench data. In line with expectations, we found that the two teeth share most of the temporal dynamics in gene expression despite heterochronies, which defines a core developmental program for making a molar. We found, surprisingly, just one specifically expressed gene but evidenced a small set of biased genes (enriched for transcription factors), constantly biased ever since the specification of lower and upper jaw. This argues for quantitative differences in gene expression modulating the core program, on top of the recognized qualitative bias (specific genes). Moreover, two findings stand against two common assumptions in comparative developmental gene expression: 1) that gene expression differences should mainly be of regulatory origin as we evidence that pervasive expression differences between lower and upper molar germ are at least in part due to a difference in the relative quantity of mesenchyme with no further need for intracellular differences in regulation; 2) that gene expression differences should increase with time as embryos/organs progress in differentiation (funnel pattern) as we demonstrate an early peak of difference (inverted hourglass pattern), when developmental processes are transiently most different. Finally our findings enable us to draw up a scenario of how the upper molar makes an additional row of cusps. More generally, our study shows that cellular proportions largely shape whole organ transcriptomes and are also responsible for transcriptomic heterochronies, which will be of interest for the understanding of gene expression evolution. SOURCE: Marie Semon (marie.semon@ens-lyon.fr) - LBMC ENS de Lyon