About

Cecilia B. Moens is an Affiliate Professor in the Department of Biology at the University of Washington and a Member in the Division of Basic Science at the Fred Hutchinson Cancer Research Center. Her research focuses on understanding how genes control cell-cell interactions that underlie the development and regeneration of neural circuits in the embryonic brain. Specifically, she investigates mechanisms of neural topographic map formation in the context of the vagus nerve, which facilitates neuronal communication between visceral organs and the brain, as well as other axon guidance events. Her laboratory utilizes the transparent zebrafish embryo as a model system, taking advantage of its accessibility to genetic manipulation and high-resolution imaging of individual neurons, their axons, and activity in vivo. Cecilia Moens received her B.Sc. in Biology from York University in Toronto, Canada, in 1987, and her Ph.D. in Medical and Molecular Genetics from the University of Toronto in 1993. She completed post-doctoral training with Charles Kimmel at the Institute of Neuroscience at the University of Oregon before joining the faculty at the Fred Hutchinson Cancer Research Center in 1998.

Research topics

• Cell biology
• Biology
• Genetics
• Neuroscience
• Immunology
• Anatomy
• Microbiology
• Computational biology
• Evolutionary biology

Selected publications

• A single-cell time-lapse of mouse prenatal development from gastrula to birth

  Nature · 2024 · 165 citations

  • Biology
  • Genetics
  • Evolutionary biology

  from earlier timepoints, to construct a rooted tree of cell-type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal shifts in cell states are observed within one hour of birth and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.

  PublisherOA PDFDOI

• Pluripotency of a founding field: rebranding developmental biology

  Development · 2024-02-01 · 6 citations

  articleOpen access

  The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional funding apparatuses, frameworks for interdisciplinary innovative collaborations, pedagogical access, improved science communication, increased diversity and inclusion, and equity of resources to provide maximal impact to the community.

  PublisherOA PDFDOI

• Position-independent functional refinement within the vagus motor topographic map

  Cell Reports · 2024-09-24 · 8 citations

  articleOpen accessSenior author

  Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse muscle and organ targets in the head and viscera for brain-body communication. It remains elusive how neighboring motor neurons with different fixed peripheral axon targets develop the separate somatodendritic (input) connectivity they need to generate spatially precise body control. Here, we show that vagus motor neurons in the zebrafish indeed generate spatially appropriate peripheral responses to focal sensory stimulation even when they are transplanted into ectopic positions within the topographic map, indicating that circuit refinement occurs after the establishment of coarse topography. Refinement depends on motor neuron synaptic transmission, suggesting that an experience-dependent periphery-to-brain feedback mechanism establishes specific input connectivity among intermingled motor populations.

  PublisherDOI

• Embryo-scale reverse genetics at single-cell resolution

  Nature · 2023-11-15 · 67 citations

  articleOpen access

  . A majority of these data, however, has been collected from wild-type embryos without an appreciation for the latent variation that is present in development. Here we present the 'zebrafish single-cell atlas of perturbed embryos': single-cell transcriptomic data from 1,812 individually resolved developing zebrafish embryos, encompassing 19 timepoints, 23 genetic perturbations and a total of 3.2 million cells. The high degree of replication in our study (eight or more embryos per condition) enables us to estimate the variance in cell type abundance organism-wide and to detect perturbation-dependent deviance in cell type composition relative to wild-type embryos. Our approach is sensitive to rare cell types, resolving developmental trajectories and genetic dependencies in the cranial ganglia neurons, a cell population that comprises less than 1% of the embryo. Additionally, time-series profiling of individual mutants identified a group of brachyury-independent cells with strikingly similar transcriptomes to notochord sheath cells, leading to new hypotheses about early origins of the skull. We anticipate that standardized collection of high-resolution, organism-scale single-cell data from large numbers of individual embryos will enable mapping of the genetic dependencies of zebrafish cell types, while also addressing longstanding challenges in developmental genetics, including the cellular and transcriptional plasticity underlying phenotypic diversity across individuals.

  PublisherOA PDFDOI

• Position-independent functional refinement within the vagus motor topographic map

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-09-13 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Motor neurons in the central nervous system often lie in a continuous topographic map, where neurons that innervate different body parts are spatially intermingled. This is the case for the efferent neurons of the vagus nerve, which innervate diverse muscle and organ targets in the head and viscera for brain-body communication. It remains elusive how neighboring motor neurons with different fixed peripheral axon targets develop the separate somatodendritic (input) connectivity they need to generate spatially precise body control. Here we show that vagus motor neurons in the zebrafish indeed generate spatially appropriate peripheral responses to focal sensory stimulation even when they are transplanted into ectopic positions within the topographic map, indicating that circuit refinement occurs after the establishment of coarse topography. Refinement depends on motor neuron synaptic transmission, suggesting that an experience-dependent periphery-to-brain feedback mechanism establishes specific input connectivity amongst intermingled motor populations.

  PublisherOA PDFDOI

• A single-cell transcriptional timelapse of mouse embryonic development, from gastrula to pup

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-04-05 · 22 citations

  preprintOpen access

  Abstract The house mouse, Mus musculus , is an exceptional model system, combining genetic tractability with close homology to human biology. Gestation in mouse development lasts just under three weeks, a period during which its genome orchestrates the astonishing transformation of a single cell zygote into a free-living pup composed of >500 million cells. Towards a global framework for exploring mammalian development, we applied single cell combinatorial indexing (sci-*) to profile the transcriptional states of 12.4 million nuclei from 83 precisely staged embryos spanning late gastrulation (embryonic day 8 or E8) to birth (postnatal day 0 or P0), with 2-hr temporal resolution during somitogenesis, 6-hr resolution through to birth, and 20-min resolution during the immediate postpartum period. From these data (E8 to P0), we annotate dozens of trajectories and hundreds of cell types and perform deeper analyses of the unfolding of the posterior embryo during somitogenesis as well as the ontogenesis of the kidney, mesenchyme, retina, and early neurons. Finally, we leverage the depth and temporal resolution of these whole embryo snapshots, together with other published data, to construct and curate a rooted tree of cell type relationships that spans mouse development from zygote to pup. Throughout this tree, we systematically nominate sets of transcription factors (TFs) and other genes as candidate drivers of the in vivo differentiation of hundreds of mammalian cell types. Remarkably, the most dramatic shifts in transcriptional state are observed in a restricted set of cell types in the hours immediately following birth, and presumably underlie the massive changes in physiology that must accompany the successful transition of a placental mammal to extrauterine life.

  PublisherOA PDFDOI

• Development and regeneration of the vagus nerve

  Seminars in Cell and Developmental Biology · 2023-08-01 · 10 citations

  reviewOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• mTOR-regulated Mitochondrial Metabolism Limits Mycobacterium-induced Cytotoxicity

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-01-30 · 5 citations

  preprintOpen access

  ABSTRACT Necrosis of macrophages in the tuberculous granuloma represents a major pathogenic event in tuberculosis. Through a zebrafish forward genetic screen, we identified the mTOR kinase, a master regulator of metabolism, as an early host resistance factor in tuberculosis. We found that mTOR complex 1 protects macrophages from mycobacterium-induced death by enabling infection-induced increases in mitochondrial energy metabolism fueled by glycolysis. These metabolic adaptations are required to prevent mitochondrial damage and death caused by the secreted mycobacterial virulence determinant ESAT-6. Thus, the host can effectively counter this early critical mycobacterial virulence mechanism simply by regulating energy metabolism, thereby allowing pathogen-specific immune mechanisms time to develop. Our findings may explain why Mycobacterium tuberculosis , albeit humanity’s most lethal pathogen, is successful in only a minority of infected individuals.

  PublisherOA PDFDOI

• mTOR-regulated mitochondrial metabolism limits mycobacterium-induced cytotoxicity

  Cell · 2022 · 70 citations

  • Biology
  • Microbiology
  • Cell biology

  Necrosis of macrophages in the granuloma, the hallmark immunological structure of tuberculosis, is a major pathogenic event that increases host susceptibility. Through a zebrafish forward genetic screen, we identified the mTOR kinase, a master regulator of metabolism, as an early host resistance factor in tuberculosis. We found that mTOR complex 1 protects macrophages from mycobacterium-induced death by enabling infection-induced increases in mitochondrial energy metabolism fueled by glycolysis. These metabolic adaptations are required to prevent mitochondrial damage and death caused by the secreted mycobacterial virulence determinant ESAT-6. Thus, the host can effectively counter this early critical mycobacterial virulence mechanism simply by regulating energy metabolism, thereby allowing pathogen-specific immune mechanisms time to develop. Our findings may explain why Mycobacterium tuberculosis, albeit humanity's most lethal pathogen, is successful in only a minority of infected individuals.

  PublisherDOI

• Deep molecular, cellular and temporal phenotyping of developmental perturbations at whole organism scale

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-08-05 · 22 citations

  preprintOpen access

  Abstract The maturation of single cell transcriptomic technologies has facilitated the generation of comprehensive cellular atlases from whole embryos. A majority of this data, however, has been collected from wild type embryos without an appreciation for latent variation present in development. Here we present single cell transcriptomic data from 1812 individually resolved developing zebrafish embryos, encompassing 19 time points, 23 genetic perturbations, and totaling 3.2M cells. The high degree of replication in our study (8 or more embryos per condition) allows us to estimate the variance in cell type abundance organism-wide and to detect perturbation-dependent deviance in cell type composition relative to wild type embryos. Our approach is sensitive to rare cell types, resolving developmental trajectories and genetic dependencies in the cranial ganglia neurons, a cell population that comprises less than 1% of the embryo. Additionally, time-series profiling of individual mutants identified a group of brachyury -independent cells with strikingly similar transcriptomes to notochord sheath cells, leading to new hypotheses about the origins of the skull. We anticipate that standardized collection of high-resolution, organism-scale single cell data from large numbers of individual embryos will enable mapping the genetic dependencies of zebrafish cell types, while also addressing long-standing challenges in developmental genetics, including the cellular and transcriptional plasticity underlying phenotypic diversity across individuals.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HD037909

  NIH · $2.7M · 2012

• Discovery of sensorimotor connectivity mechanisms in a continuous topographic map

  NIH · $493k · 2022–2025

• In vivo cell-cell interactions regulating melanoma metastatic cell behaviors

  NIH · $421k · 2015–2017

• Topographic mapping by cranial motor neurons - Renewal - Resubmission - 1

  NIH · $2.9M · 2018–2030

• Mechanisms of Tangential Neuron Migration

  NIH · $412k · 2013–2018

Frequent coauthors

• Luyuan Pan

  Institute of Hydrobiology

  50 shared

• Hung‐Hsiang Yu

  Institute of Cellular and Organismic Biology, Academia Sinica

  36 shared

• P. Taylur

  26 shared

• Janet Rossant

  Hospital for Sick Children

  23 shared

• Holly A. Rikhof

  Howard Hughes Medical Institute

  23 shared

• Bruce W. Draper

  University of California, Davis

  22 shared

• Hilary A. Kemp

  University of Alberta

  21 shared

• Rafael E. Hernandez

  Infectious Disease Research Institute

  20 shared

Education

• B.S.

  York University

  1987

• Ph.D., Medical and Molecular Genetics

  University of Toronto

  1993