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.
Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility.
Neurogastroenterol Motil. 2018 May 02;:e13351
Authors: Ganz J, Baker RP, Hamilton MK, Melancon E, Diba P, Eisen JS, Parthasarathy R
BACKGROUND: Normal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Previous image analysis approaches have successfully extracted properties related to the temporal frequency of motility modes, but robust measures of contraction magnitude, especially from in vivo image data, remain challenging to obtain.
METHODS: We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motion.
KEY RESULTS: We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild types.
CONCLUSIONS & INFERENCES: Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.
PMID: 29722095 [PubMed - as supplied by publisher]
Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.
Development. 2018 Feb 23;145(4):
Authors: Troll JV, Hamilton MK, Abel ML, Ganz J, Bates JM, Stephens WZ, Melancon E, van der Vaart M, Meijer AH, Distel M, Eisen JS, Guillemin K
Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer.
PMID: 29475973 [PubMed - in process]