Deciphering an Alternative Developmental Morphospace

During early animal embryonic development, a simple collective of cells is transformed into a complex, multilayered structure. At first, the specification of a mouth and an opposite side defines a main body axis. Characteristic animal body plan features, such as the developing nervous system, gut and limbs, are spatially arranged along this reference line. Initial body axis specification is deeply conserved across the animal kingdom from humans to sea anemones, since the same or functionally similar genes orchestrate associated processes. Yet, embryonic development is also guided by species-specific, external (e.g. maternally deposited) factors or signals. Here, we aim to remove or diminish the influence of such external cues to uncover how isolated embryonic cells can autonomously develop or self-organize into a functional animal. This can be achieved by the manual dissociation and re-aggregation of early embryos in a (cell culture) dish, resulting in the scrambling of any pre-existing patterning or positional information. Pioneering experiments in the sea anemone Nematostella have shown that initial body axis formation in such embryonic aggregates occurs via different cell collective movement dynamics than in the natural embryo while still yielding the same outcome: a functional animal. This may suggest that embryonic cells possess a broader, inherent developmental potential of main axis formation. Hence, only when removing the stereotypical (external) factors guiding natural embryonic development can this otherwise hidden cell- inherent potential be studied. The goal of this project is to reveal common principles guiding the generation and diversification of animal body plans during evolution, resulting from the interplay between the embryonic cell-inherent potential and externally provided factors. Specifically, we will identify how and which cell- to tissue-level interactions (e.g. attachment and signaling) facilitate body axis formation in aggregates of sea anemone embryos. We will further establish embryonic aggregates in the jellyfish Clytia, a species that exhibits a distinct mode of natural development than the sea anemone Nematostella. This will enable a direct comparison of both aggregated systems to potentially uncover developmental similarities not found in the embryo. Finally, we will leverage our experimental data to derive key biophysical parameters and generate a computational 3D model explaining aggregate developmental dynamics. Compared to humans, Nematostella and Clytia exhibit similar overall gene regulatory logic of initial body axis formation, despite the large evolutionary distance. Therefore, this project holds promise to uncover novel, fundamental mechanisms governing the generation of animal form.