Bioelectric regulation of embryonic pattern formation in Xenopus laevis
Abstract: The goal of embryonic development is to produce a functional and
anatomically correct organism. To achieve this, cells must undergo complicated
developmental trajectories that are dictated by genetic, chemical, and environmental
factors. One important way cells respond to their environment is by modulating
transmembrane voltage potentials through the actions of ion channels and pumps... read more. These
voltage potentials provide instructional information during embryogenesis that regulates
important cellular behaviors, and ultimately anatomical patterning. Recent studies
highlight the importance of endogenous bioelectric signaling during development, and
demonstrate that alteration of these signals has severe consequences for cell fate and cell
positioning. However, how and when bioelectric signals function and integrate with
biochemical and genetic signaling to direct embryonic patterning is just beginning to be
understood. We took advantage of the externally developing frog, Xenopus laevis, to
investigate the role of bioelectricity during embryogenesis. To compliment current in vivo
studies, we designed a novel assay for studying bioelectricity in vitro. We demonstrate
that altering membrane potential in two separate organ systems disrupts normal organ
patterning. In the Xenopus cement gland, both depolarization and hyperpolarization induce
ectopic cement gland formation via transduction through calcium signaling. With regards to
heart development, we provide the first spatio-temporal characterization of the clinically
important ion channel hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4)
in Xenopus. We show that altering HCN4 channel function disrupts heart positioning but not
differentiation. These positional defects are caused by the spatial disruption of canonical
patterning genes. These data highlight how bioelectric signaling acts as a key mediator of
patterning decisions during embryogenesis, with implications for biomedical applications
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Biology.
Advisor: Kelly McLaughlin.
Committee: Michael Levin, David Kaplan, and Stephen Fuchs.
Keyword: Developmental biology.read less