Genetics of developmental timing and size control in vertebrates

• Applicant: Dr. Ali Seleit, Ph.D.
• Subject Area: Developmental Biology ; General Genetics and Functional Genome Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564092250

Despite broad conservation of molecular players and developmental mechanisms, the pace of development varies considerably across vertebrates. This cross-species diversity contrasts with the tightly constrained intra-species variation in the duration of embryogenesis and argues that developmental rate is both heritable and evolvable. But what controls the rate of embryonic development in vertebrates? And, more importantly, how is this information encoded at the genetic level? I propose addressing these questions using a unique vertebrate system that I am at the forefront of developing. The comparative developmental genetics approach I will use relies on exploiting the natural variation of developmental timing and organismal size that I found across the Oryzias fish genus. The compact genomes of these fishes, their genetic amenability and our ability to produce genetic hybrids provides us with a highly tractable system to address the genetic basis of phenotypic variability in complex developmental traits. By leveraging the power of in vivo quantitative phenotyping, quantitative trait loci (QTL) mapping and comparative multi-omics, I will dissect the genetic basis of developmental timing and size-scaling in vivo and within a well-defined evolutionary context. My aim is to arrive at a genetic and mechanistic understanding of developmental timing and size control in vertebrates and to elucidate the underlying basis of the strong scaling link between these complex traits. The highly conserved process of body axis segmentation in vertebrates is an especially useful system to address the above mentioned questions as temporal and spatial components can be precisely quantified and are known to be species-specific. The system relies on a series of morphogen gradients expressed in the presomitic mesoderm coupled to oscillatory gene expression (‘the segmentation clock’), with the period of oscillation matching the timing of addition of a new pair of somites. The period of the segmentation clock linearly correlates with the length of embryogenesis in diverse species making it an excellent system to quantitatively phenotype developmental timing. The strength of this proposal lies in its in vivo comparative developmental approach utilizing eight Oryzias fish species that cover the phylogenetic and phenotypic space of both developmental timing (2-fold) and size (4-fold in length) across the clade. This untapped system I am pioneering will allow my lab to uncover the genetic basis of developmental timing and size scaling. My Emmy-Noether proposal has 3 objectives i) establish embryonic, genomic and transgenic resources in uncharacterized Oryzias species, use these resources to ii) uncover the global regulators and mechanisms governing developmental timing and size control iii) decipher the genetic basis of developmental timing and size control and understand how evolutionary tinkering with developmental programs leads to variation in both traits.

• DFG Programme: Emmy Noether Independent Junior Research Groups