Project Summary
Signaling from chemosensory neurons regulates changes in animal physiology and behavior in response to
environmental and social cues. Sensory neuroanatomy is so broadly conserved in nematodes that, based on
morphology and cell body position, functionally homologous chemosensory neurons have been identified
across widely divergent nematode genera, including the well-studied free living nematode Caenorhabditis
elegans, the skin-penetrating human parasite Strongyloides stercoralis, and the predatory nematode Pristionchus
pacificus.
Despite this homology, little is known about the conservation of the developmental and genetic programs that
produce individual chemosensory neurons and maintain or differentiate their function. To what extent do
anatomically homologous neurons share conserved chemosensory function? And to what extent does
anatomical homology reflect a common developmental program? We will answer these questions by mapping
the cell lineages that give rise to chemosensory neurons, determining the extent to which positionally
homologous chemosensory neurons are specified by conserved transcriptional regulators, and identifying
conserved chemosensory function. We will achieve this by developing a novel 3D style transfer convolutional
neural network (stCNN) to automate the identification of major cellular features such as the nucleus and cell
membrane in transmitted light imaging with differential interference contrast (DIC). We will then use this tool
to reconstruct the embryonic lineages of S. stercoralis and P. pacificus, map the expression of known regulators of
chemosensory neural identity to these lineages, and assess the conservation of function between homologous
chemosensory neurons by performing laser cell ablations and single-worm chemotaxis assays.
This work has direct relevance to human health, since chemosensation regulates many aspects of development,
physiology, and behavior in S. stercoralis and other human-parasitic nematodes. Parasitic nematodes infect over
a billion people worldwide and cause some of the most common and devastating neglected tropical diseases,
particularly in low-resource settings. Our multi-species approach will allow us to determine which aspects of
nematode chemosensory system development and function are broadly conserved, and which contain species-
specific adaptations that drive species-specific behaviors, including parasitic behaviors. Furthermore, the
automated reconstruction of cell lineages from DIC images will be an enabling tool of broad value. The ability
to map new developmental lineages without transgenesis will be especially transformative in the study of
human-parasitic nematodes such as hookworms that are not amenable to genetic manipulation, and can be
extended to non-nematode species, including early-stage vertebrate embryos.