The sea squirt Ciona intestinalis is member of the urochordates, the closest living relatives of the vertebrates. Ciona tadpoles provide a favorable system for studying the evolutionary origins of key vertebrate innovations such as cranial placodes and neural crest. There are four major sensory cell types that arise from the neural plate border, which is the source of placodes and neural crest in vertebrates. The Ciona system is ideally suited to elucidate the gene networks and developmental mechanisms underlying the specification of all four sensory cell types: hair cells (head), GnRH-expressing aATENs (trunk), pATENs and BTNs (tail). The detailed understanding of these cell types should provide new insights into the evolutionary origins and developmental mechanisms underlying the specification of comparable cell types derived from placodes and neural crest in vertebrates, particularly placodes. During the preceding funding period we obtained evidence that the hair cells and aATENs arise from a proto-placodal territory straddling the anterior border of the presumptive neural tube. The aATENs possess dual chemosensory and neurosecretory properties, suggesting they represent an ancestral cell type that produced specialized cell types through a process of ?cellular subfunctionalization? during the evolution of the vertebrates. The pATENs and BTNs possess similarities with derivatives of the neural crest in vertebrates, such as dorsal root ganglia. There are two over-arching goals of the proposed study: (i) explore the specification, differentiation, and relatedness of hair cells, aATENs, pATENs, and BTNs in the Ciona tadpole; and, (ii) explore the process of cellular subfunctionalization, whereby ancestral sensory cell types in Ciona produce multiple specialized cell types forming neuronal circuits in vertebrates.

Public Health Relevance

Defects in the development of placodes and neural crest are responsible for a broad spectrum of human diseases. The detailed elucidation of the developmental mechanisms that control the specification of these embryonic tissues is critical to the long-range goal of prenatal diagnosis and treatment. Given the close evolutionary kinship of Ciona and vertebrates, it is likely that the lessons learned in the simple Ciona system will inform our understanding of comparable processes in vertebrates.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Riddle, Robert D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Princeton University
Schools of Arts and Sciences
United States
Zip Code
Treen, Nicholas; Heist, Tyler; Wang, Wei et al. (2018) Depletion of Maternal Cyclin B3 Contributes to Zygotic Genome Activation in the Ciona Embryo. Curr Biol 28:1150-1156.e4
Horie, Ryoko; Hazbun, Alex; Chen, Kai et al. (2018) Shared evolutionary origin of vertebrate neural crest and cranial placodes. Nature 560:228-232
Navarrete, Ignacio A; Levine, Michael (2016) Nodal and FGF coordinate ascidian neural tube morphogenesis. Development 143:4665-4675
Farley, Emma K; Olson, Katrina M; Zhang, Wei et al. (2016) Syntax compensates for poor binding sites to encode tissue specificity of developmental enhancers. Proc Natl Acad Sci U S A 113:6508-13
Farley, Emma K; Olson, Katrina M; Zhang, Wei et al. (2015) Suboptimization of developmental enhancers. Science 350:325-8
Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N et al. (2015) The pre-vertebrate origins of neurogenic placodes. Nature 524:462-5
Gainous, T Blair; Wagner, Eileen; Levine, Michael (2015) Diverse ETS transcription factors mediate FGF signaling in the Ciona anterior neural plate. Dev Biol 399:218-25
Farley, Emma K; Olson, Katrina M; Levine, Michael S (2015) Regulatory Principles Governing Tissue Specificity of Developmental Enhancers. Cold Spring Harb Symp Quant Biol 80:27-32
Diogo, Rui; Kelly, Robert G; Christiaen, Lionel et al. (2015) A new heart for a new head in vertebrate cardiopharyngeal evolution. Nature 520:466-73
Levine, Michael (2014) The contraction of time and space in remote chromosomal interactions. Cell 158:243-244

Showing the most recent 10 out of 16 publications