Professor, Department of Biology
Ph.D. Brandeis University
B.S. Utah State
Research Interests: Specification and patterning of neurons and neural crest cells in embryonic zebrafish
Overview: The vertebrate nervous system is composed of a large number of neurons with diverse characteristics. My lab is interested in how neuronal diversity is generated during development: how are the correct number of cells specified for specific neuronal fates at particular times and in particular locations? Most of our attention has been focused on a small, early-developing set of individually identified spinal motoneurons and on the neural crest, a transient embryonic cell population that generates a diverse set of derivatives, including the neurons and glia of the peripheral nervous system. We use a combined cellular, molecular and genetic approach to learn the mechanisms underlying cell fate specification. For example, we study the timing of critical events during development of motoneurons and neural crest cells by labeling individual cells and following their development in living embryos and by transplanting individual cells to new locations. We are isolating genes encoding molecules that may regulate motoneuron and neural crest development and testing the roles of the proteins encoded by these genes during motoneuron and neural crest specification and differentiation. We are also isolating mutations that alter motoneuron or neural crest cell fate with the goal of identifying new genes involved in the development of these cells.
The enteric nervous system promotes intestinal health by constraining microbiota composition.
PLoS Biol. 2017 Feb;15(2):e2000689
Authors: Rolig AS, Mittge EK, Ganz J, Troll JV, Melancon E, Wiles TJ, Alligood K, Stephens WZ, Eisen JS, Guillemin K
Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health.
PMID: 28207737 [PubMed - in process]
Best practices for germ-free derivation and gnotobiotic zebrafish husbandry.
Methods Cell Biol. 2017;138:61-100
Authors: Melancon E, Gomez De La Torre Canny S, Sichel S, Kelly M, Wiles TJ, Rawls JF, Eisen JS, Guillemin K
All animals are ecosystems with resident microbial communities, referred to as microbiota, which play profound roles in host development, physiology, and evolution. Enabled by new DNA sequencing technologies, there is a burgeoning interest in animal-microbiota interactions, but dissecting the specific impacts of microbes on their hosts is experimentally challenging. Gnotobiology, the study of biological systems in which all members are known, enables precise experimental analysis of the necessity and sufficiency of microbes in animal biology by deriving animals germ-free (GF) and inoculating them with defined microbial lineages. Mammalian host models have long dominated gnotobiology, but we have recently adapted gnotobiotic approaches to the zebrafish (Danio rerio), an important aquatic model. Zebrafish offer several experimental attributes that enable rapid, large-scale gnotobiotic experimentation with high replication rates and exquisite optical resolution. Here we describe detailed protocols for three procedures that form the foundation of zebrafish gnotobiology: derivation of GF embryos, microbial association of GF animals, and long-term, GF husbandry. Our aim is to provide sufficient guidance in zebrafish gnotobiotic methodology to expand and enrich this exciting field of research.
PMID: 28129860 [PubMed - in process]
Molecular fingerprinting delineates progenitor populations in the developing zebrafish enteric nervous system.
Dev Dyn. 2016 Aug 26;
Authors: Taylor CR, Montagne WA, Eisen JS, Ganz J
Background To understand the basis of nervous system development, we must learn how multipotent progenitors generate diverse neuronal and glial lineages. We addressed this issue in the zebrafish enteric nervous system (ENS), a complex neuronal and glial network that regulates essential intestinal functions. Little is currently known about how ENS progenitor subpopulations generate enteric neuronal and glial diversity. Results We identified temporally and spatially dependent progenitor subpopulations based on coexpression of three genes essential for normal ENS development: phox2bb, sox10, and ret. Our data suggest that combinatorial expression of these genes delineates three major ENS progenitor subpopulations, (1) phox2bb+/ret-/sox10-, (2) phox2bb+/ret+/sox10-, and (3) phox2bb+/ret+/sox10+, that reflect temporal progression of progenitor maturation during migration. We also found that differentiating zebrafish neurons maintain phox2bb and ret expression, and lose sox10 expression. Conclusion Our data show that zebrafish enteric progenitors constitute a heterogeneous population at both early and late stages of ENS development and suggest that marker gene expression is indicative of a progenitor's fate. We propose that a progenitor's expression profile reveals its developmental state: "younger" wave front progenitors express all three genes, whereas more mature progenitors behind the wave front selectively lose sox10 and/or ret expression, which may indicate developmental restriction. This article is protected by copyright. All rights reserved.
PMID: 27565577 [PubMed - as supplied by publisher]