Biology subjects

Rogers, K. W.

Publications and source records attributed to Rogers, K. W..

5 recordsLinked to original sources

bioRxiv2026

A transgenic zebrafish for direct optogenetic activation of FGF/ERK signaling

Dynamic FGF/ERK signaling plays key roles in development, regeneration, and disease. We recently developed a zebrafish-optimized optogenetic tool, bOpto-FGF, that enables reversible activation of FGF/ERK signaling in response to blue light ([~]455 nm) by fusing a zebrafish receptor tyrosine kinase domain to the blue light-dimerizing LOV domain. Previously, this tool was introduced into zebrafish embryos by mRNA injection. Here, we develop Tg(ubi:bOpto-FGF), a novel transgenic zebrafish ubiquitously expressing bOpto-FGF, to streamline experimental workflows. We demonstrate robust blue light-mediated activation of FGF/ERK signaling and FGF target gene expression in early gastrulation-stage Tg(ubi:bOpto-FGF) embryos. Light-mediated signaling activation at this stage is more spatially uniform in transgenics compared to mRNA-injected embryos, and ectopic signaling in response to continuous light exposure is activated within 3 minutes and maintained for at least 75 minutes. Further, Tg(ubi:bOpto-FGF) heterozygotes are light-responsive from late blastula stages through at least 24 hours post-fertilization. Finally, we demonstrate light-mediated spatially localized FGF/ERK signaling activation within 1 minute in the head, trunk, and tail at 1 day post-fertilization. This transgenic line provides a powerful and convenient new strategy for spatiotemporal manipulation of FGF/ERK signaling dynamics in the vertebrate zebrafish model. Summary StatementNovel transgenic zebrafish provides precise optogenetic control of a key developmental signaling pathway in vivo

developmental biology↗

bioRxiv2025

An optogenetic toolkit for robust activation of FGF, BMP, and Nodal signaling in zebrafish

Cell signaling regulates a wide range of biological processes including development, homeostasis, and disease. Accessible technologies to precisely manipulate signaling have important applications in basic and translational research. Here, we present an optogenetic toolkit for signaling manipulation in zebrafish embryos. We introduce a zebrafish-optimized optogenetic FGF signaling activator and a single-transcript Nodal signaling activator, and assess them together with a previously established BMP signaling activator. We thoroughly characterize this suite of tools and demonstrate light-dependent spatiotemporal control of signaling in vivo. In response to [~]455 nm (blue) light, zebrafish receptor kinase domains fused to blue light-dimerizing LOV domains enable robust signaling activation with minimal inadvertent activity in the dark or at wavelengths over 495 nm. Each optogenetic tool initiates pathway-specific signaling and activates known target genes. Signaling is activated with rapid on/off kinetics, and activation strength can be tuned by adjusting light irradiance. Finally, we demonstrate spatially localized signaling activation in vivo. Together, our results establish this optogenetic toolkit as a potent experimental platform and provide guidelines for rapid, direct, and adjustable activation of FGF, BMP, and Nodal signaling in zebrafish embryos.

developmental biology↗

bioRxiv2022

Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator

BMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan Nematostella vectensis, several of which were conserved in Drosophila and Xenopus. Our ChIP-Seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in Nematostella are directly controlled by BMP signaling. Among the so far uncharacterized BMP-dependent transcription factors and signaling molecules we identified several, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules, zswim4-6, encodes a novel nuclear modulator of the pSMAD1/5 gradient potentially promoting BMP-dependent gene repression. Strikingly, overexpression of the zebrafish homologue zswim5 suggests that its effect on the pSMAD1/5 gradient is conserved between anthozoan Cnidaria and Bilateria.

developmental biology↗

bioRxiv2018

A conserved regulatory program drives emergence of the lateral plate mesoderm

Cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolated a pan-LPM enhancer in the zebrafish draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captured the dynamic LPM emergence as lineage-restricted mesendoderm field. The drl pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncovered specific drl reporter activity in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.

developmental biology↗

bioRxiv2017

Paracrine Activin-A Signaling Promotes Melanoma Growth And Metastasis Through Immune Evasion

The secreted growth factor Activin-A of the TGF{beta} family and its receptors can promote or inhibit several cancer hallmarks including tumor cell proliferation and differentiation, vascularization, lymphangiogenesis and inflammation. However, a role in immune evasion and its relationship with tumor-induced muscle wasting and tumor vascularization, and the relative contributions of autocrine versus paracrine Activin signaling remain to be evaluated. To address this, we compared the effects of truncated soluble Activin receptor II B as a ligand trap, or constitutively active mutant type IB receptor versus secreted Activin-A or the related ligand Nodal in mouse and human melanoma cell lines and tumor grafts. We found that while cell-autonomous receptor activation arrested tumor cell proliferation, Activin-A secretion stimulated melanoma cell dedifferentiation and tumor vascularization by functional blood vessels, and it increased primary and metastatic tumor burden and muscle wasting. Importantly, in mice with impaired adaptive immunity, the tumor-promoting effect of Activin-A was lost despite sustained vascularization and cachexia, suggesting that Activin-A promotes melanoma progression by inhibiting anti-tumor immunity. Paracrine Activin-A signaling emerges as a potential target for personalized therapies, both to reduce cachexia and to enhance the efficacy of immunotherapies.

cancer biology↗