Mapping the Origins of the Vertebrate Brain

Abstract

Transcriptomic maps of the brain that reflect neuroanatomy are critical resources to study neuroscience and neurodevelopment. Here we present a transcriptomic map of the larval brain of the ascidian Ciona intestinalis, which represents a close approximation of the vertebrate ancestor. Through iterative use of cell type specific reporters, we compiled the location and morphology of the majority of the neural cell types in the larval brain identified via single cell transcriptomics. The resulting map reveals the transcriptomic organization of the larval brain at the level of individual neurons that comprise each cell type. We used this information to describe a putative neural circuit that integrates gravity and light to mediate age-dependent changes in gravitaxis behavior in the larvae. We found that the gravity sensitive otolith cell is associated with both excitatory and inhibitory neurons that synapse to the same group of relay neurons. Implicated in modulating the circuit to elicit behavioral changes are the interaction between coronet cells, which represent a forerunner of the vertebrate hypothalamus, and the inhibitory neurons associated with the otolith, and a novel photosensory function in coronet cells. We further examined the specification of coronet cells and the inhibitory interneurons, and uncovered key genetic interactions and fate determinants that underlie their development. Our work provides insights into the evolution of the vertebrate hypothalamus, and highlights the value of a transcriptomic brain map by demonstrating its utility in the context of neuroscience, neurodevelopment, and evolution.