Abstract The bone-morphogenetic protein (BMP)-SMAD signal transduction pathway regulates fundamental cellular processes such as fate specification, tissue patterning, and stem cell homeostasis across metazoans and has a conserved signaling architecture. However, the quantitative dynamics of SMAD signaling and regulatory strategies governing pathway activity show a wide range of variation across developmental and stem-cell systems. In the present review, we summarize insights from six major biological contexts—Drosophila embryo, germline stem cells, and the larval and pupal wing discs; the Danio rerio (zebrafish) embryo; and human pluripotent stem cells—to compare how BMP signals are measured, manipulated, modeled, and integrated. We begin by outlining the canonical BMP signaling pathway and the mechanisms of BMP gradient formation across developmental systems, highlighting how conserved pathway components contribute to the formation of system-specific spatial profiles. We then summarize intracellular Smad dynamics and how endogenous pathway dynamics are measured through quantitative imaging of the phosphorylated Smad. Next, we examine how BMP signaling is interpreted through tiered transcriptional responses of downstream target genes. Next, we summarize the mechanistic and computational models of integrated gradient formation, signal transduction, and gene regulation across the presented systems. These insights reveal unifying design principles and performance objectives that govern BMP-SMAD signaling across species and cell types and frame open questions for future cross-species and translational studies.
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Quantitative insights in tissue growth and morphogenesis with optogenetics
Abstract Cells communicate with each other to jointly regulate cellular processes during cellular differentiation and tissue morphogenesis. This multiscale coordination arises through the spatiotemporal activity of morphogens to pattern cell signaling and transcriptional factor activity. This coded information controls cell mechanics, proliferation, and differentiation to shape the growth and morphogenesis of organs. While many of the molecular components and physical interactions have been identified in key model developmental systems, there are still many unresolved questions related to the dynamics involved due to challenges in precisely perturbing and quantitatively measuring signaling dynamics. Recently, a broad range of synthetic optogenetic tools have been developed and employed to quantitatively define relationships between signal transduction and downstream cellular responses. These optogenetic tools can control intracellular activities at the single cell or whole tissue scale to direct subsequent biological processes. In this brief review, we highlight a selected set of studies that develop and implement optogenetic tools to unravel quantitative biophysical mechanisms for tissue growth and morphogenesis across a broad range of biological systems through the manipulation of morphogens, signal transduction cascades, and cell mechanics. More generally, we discuss how optogenetic tools have emerged as a powerful platform for probing and controlling multicellular development.
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- PAR ID:
- 10466267
- Date Published:
- Journal Name:
- Physical Biology
- Volume:
- 20
- Issue:
- 6
- ISSN:
- 1478-3967
- Page Range / eLocation ID:
- 061001
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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