Bioelectric regulation of embryonic pattern formation in Xenopus laevis
Pitcairn, Emily.
2017
-
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. Th... read moreese 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 and bioengineering.
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 - ID:
- ws859t44k
- To Cite:
- DCA Citation Guide EndNote
