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.
Evolution of Endothelin signaling and diversification of adult pigment pattern in Danio fishes.
PLoS Genet. 2018 Sep 18;14(9):e1007538
Authors: Spiewak JE, Bain EJ, Liu J, Kou K, Sturiale SL, Patterson LB, Diba P, Eisen JS, Braasch I, Ganz J, Parichy DM
Fishes of the genus Danio exhibit diverse pigment patterns that serve as useful models for understanding the genes and cell behaviors underlying the evolution of adult form. Among these species, zebrafish D. rerio exhibit several dark stripes of melanophores with sparse iridophores that alternate with light interstripes of dense iridophores and xanthophores. By contrast, the closely related species D. nigrofasciatus has an attenuated pattern with fewer melanophores, stripes and interstripes. Here we demonstrate species differences in iridophore development that presage the fully formed patterns. Using genetic and transgenic approaches we identify the secreted peptide Endothelin-3 (Edn3)-a known melanogenic factor of tetrapods-as contributing to reduced iridophore proliferation and fewer stripes and interstripes in D. nigrofasciatus. We further show the locus encoding this factor is expressed at lower levels in D. nigrofasciatus owing to cis-regulatory differences between species. Finally, we show that functions of two paralogous loci encoding Edn3 have been partitioned between skin and non-skin iridophores. Our findings reveal genetic and cellular mechanisms contributing to pattern differences between these species and suggest a model for evolutionary changes in Edn3 requirements for pigment patterning and its diversification across vertebrates.
PMID: 30226839 [PubMed - as supplied by publisher]
Forebrain Control of Behaviorally Driven Social Orienting in Zebrafish.
Curr Biol. 2018 Jul 21;:
Authors: Stednitz SJ, McDermott EM, Ncube D, Tallafuss A, Eisen JS, Washbourne P
Deficits in social engagement are diagnostic of multiple neurodevelopmental disorders, including autism and schizophrenia . Genetically tractable animal models like zebrafish (Danio rerio) could provide valuable insight into developmental factors underlying these social impairments, but this approach is predicated on the ability to accurately and reliably quantify subtle behavioral changes. Similarly, characterizing local molecular and morphological phenotypes requires knowledge of the neuroanatomical correlates of social behavior. We leveraged behavioral and genetic tools in zebrafish to both refine our understanding of social behavior and identify brain regions important for driving it. We characterized visual social interactions between pairs of adult zebrafish and discovered that they perform a stereotyped orienting behavior that reflects social attention . Furthermore, in pairs of fish, the orienting behavior of one individual is the primary factor driving the same behavior in the other individual. We used manual and genetic lesions to investigate the forebrain contribution to this behavior and identified a population of neurons in the ventral telencephalon whose ablation suppresses social interactions, while sparing other locomotor and visual behaviors. These neurons are cholinergic and express the gene encoding the transcription factor Lhx8a, which is required for development of cholinergic neurons in the mouse forebrain . The neuronal population identified in zebrafish lies in a region homologous to mammalian forebrain regions implicated in social behavior such as the lateral septum . Our data suggest that an evolutionarily conserved population of neurons controls social orienting in zebrafish.
PMID: 30057306 [PubMed - as supplied by publisher]