Cell Numbers Contribute to Cell Fate During Ciona Cardiopharyngeal Mesoderm Specification

The Ciona heart cell lineage can be accurately traced back to a pair of blastomeres, the B7.5 cells, that form at the 64-cell stage. In addition to the adult heart, the B7.5 cells also contribute to two tail muscle cells in the larva, as well as the muscles that form the siphons for pumping water for feeding. Because of the simplicity of this system, we have a good understanding of how the B7.5 derivatives are specified during development. However, we know less about how the Ciona embryo precisely regulates cell numbers, as well as what effects altering cell numbers will have on development. We found that cell numbers in the B7.5 lineage are controlled by a pulse of transcription of the cell cycle inhibitor Cdkn1.b. Cdkn1.b can be repressed by the paralogues Prdm1-r.a and Prdm1-r.b that are exclusively transcribed in the B7.5 cells at the 110-cell stage. We unexpectedly found that precocious arrest of cell division in the B7.5 cell lineage resulted in a reversion to tail muscle fate, even in cells that can migrate. Our work demonstrates an unexpected connection between the control of cell numbers and cell fate in development. Significance StatementThe control of cell numbers is essential to many developmental processes, but it has been relatively understudied. A clear example of this can be seen in heart development. Hearts develop from precursor cells called cardiopharyngeal mesoderm. These cells must be able to migrate and proliferate in a precise way or heart defects will occur. We took advantage of the simplicity of embryonic development in the chordate Ciona (an invertebrate closely related to vertebrates) to investigate the consequences of disrupting cell numbers on heart development. Our finding that an early arrest in cell division results in a failure of heart development has implications for similar processes in vertebrates, including humans.