Abstract
The Rosalind Franklin Society (RFS), in partnership with Mary Ann Liebert, Inc., publishers, enthusiastically congratulate our distinguished recipient of the 2023 annual
Laura Faith George, Mikaela Lynn Follmer, Emily Fontenoy, Hannah Rose Moran, Jeremy Ryan Brown, Yunus H. Ozekin, and Emily Anne Bates, “Endoplasmic Reticulum Calcium Mediates Drosophila Wing Development,” Bioelectricity 5, no. 4 (December 2023): 290–306, https://doi.org/10.1089/bioe.2022.0036.
Abstract
Background: The temporal dynamics of morphogen presentation impacts transcriptional responses and tissue patterning. However, the mechanisms controlling morphogen release are far from clear. We found that inwardly rectifying potassium (Irk) channels regulate endogenous transient increases in intracellular calcium and bone morphogenetic protein (BMP/Dpp) release for Drosophila wing development. Inhibition of Irk channels reduces BMP/Dpp signaling, and ultimately disrupts wing morphology. Ion channels impact development of several tissues and organisms in which BMP signaling is essential. In neurons and pancreatic beta cells, Irk channels modulate membrane potential to affect intracellular Ca++ to control secretion of neurotransmitters and insulin. Based on Irk activity in neurons, we hypothesized that electrical activity controls endoplasmic reticulum (ER) Ca++ release into the cytoplasm to regulate the release of BMP.
Materials and Methods: To test this hypothesis, we reduced expression of four proteins that control ER calcium, Stromal interaction molecule 1 (Stim), Calcium release-activated calcium channel protein 1 (Orai), SarcoEndoplasmic Reticulum Calcium ATPase (SERCA), small conductance calcium-activated potassium channel (SK), and Bestrophin 2 (Best2) using RNAi and documented wing phenotypes. We use live imaging to study calcium and Dpp release within pupal wings and larval wing discs. Additionally, we employed immunohistochemistry to characterize Small Mothers Against Decapentaplegic (SMAD) phosphorylation downstream of the BMP/Dpp pathway following RNAi knockdown.
Results: We found that reduced Stim and SERCA function decreases amplitude and frequency of endogenous calcium transients in the wing disc and reduced BMP/Dpp release.
Conclusion: Our results suggest control of ER calcium homeostasis is required for BMP/Dpp release, and Drosophila wing development.
Biosketch
Mikaela received her Bachelor of Science in 2019 with a focus in developmental biology. During her undergraduate career she completed a 3-year comparative study of RNAi methods in Drosophila under the supervision of her mentor, Dr. Pavithra Vivekanand. Mikaela then worked as a research technician for two years at Pennsylvania State University, studying malaria transmission and maintaining a colony of a few thousand mosquitoes in the lab of Dr. Scott Linder. Currently a 3rd year PhD Candidate in Dr. Emily Bates, lab at the University of Colorado – Anschutz Medical Campus, Mikaela is working on uncovering the machinery required to control release of the developmental morphogen BMP. Mikaela is also a first-generation student who paved her own way in her scientific career, and because of this she is dedicated to mentoring the next generation of scientists from similar backgrounds. She is the vice president and internship director of the Colorado Chapter of Clear Direction Mentoring (a non-profit) where she teaches immersive STEM internships and works to maintain chapter longevity through increasing partnerships and outreach opportunities. Mikaela plans to combine her passion for science and mentoring by one day running a research lab at a primarily undergraduate institution.