In many animal species, early embryos can continue development even when certain cells are removed. This is because other cells step in to take on new roles, in a process known as ‘transfating’. For example, 16-cell stage sea urchin embryos contain cells called micromeres, which contribute to the formation of three mesodermal cell types: skeletogenic, blastocoelar and pigment cells. When micromeres are removed, the skeletogenic and blastocoelar cells are replaced via transfating, but the pigment cells remain absent, resulting in albino embryos. Here, David McClay and colleagues use single-cell RNA sequencing to explore developmental trajectories in micromereless embryos. They show that, following micromere removal, replacement skeletogenic and blastocoelar cells originate from the early endoderm. They go on to disrupt transcription factors and signals involved in sea urchin development; these include Delta, the expression of which is delayed in embryos that lack micromeres, and Nodal, the expression of which separates the dorsal (pigment cells) and ventral (blastocoelar cells) mesoderm cell types. By modulating the time at which Delta is expressed in the micromereless embryos, the authors find that expressing Delta prior to Nodal allows replacement pigment cells to appear. Overall, this work demonstrates that the timing of developmental signals is crucial for determining the outcome of transfating potential. This raises the possibility that the addition of developmental events that inhibit transfating may result in a loss of regenerative capacity over evolutionary time.
