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Biology subjects

Wu, S. Y. C.

Publications and source records attributed to Wu, S. Y. C..

5 recordsLinked to original sources

A conserved pituitary response to tissue loss controls regeneration across vertebrates

Regenerating complex tissues requires coordination between local cellular responses and body-wide systemic signals. As a central endocrine regulator, the pituitary is well positioned to coordinate this process. Here, we identify the pituitary as an injury-responsive regulator of axolotl limb and tilapia fin regeneration. Limb loss triggered sustained transcriptional responses in the axolotl pituitary. Single-cell transcriptomics linked pituitary loss to altered gene expression in prolactin- and growth hormone-responsive limb cells. Local disruption of the prolactin receptor impaired digit formation, whereas combined hormone treatment partially restored regeneration in hypophysectomized axolotls. In tilapia, pituitary removal impaired fin regeneration and prolactin-related signaling. Mouse digits differed from axolotls and tilapia in how and when they received pituitary signals during regeneration, suggesting pituitary-dependent regrowth is evolutionarily divergent among highly regenerative vertebrates.

systems biology↗

Multi-omic characterization of axolotl perilymph-cerebrospinal fluid reveals shifts in composition during limb regeneration

The axolotl salamander can fully regenerate amputated limbs, yet the systemic consequences underlying this process remain largely understudied. Cerebrospinal fluid is an emerging signaling medium capable of communicating with both the central and peripheral nervous systems, but its composition and potential role in salamander limb regeneration have not yet been examined using modern multi-omics techniques. Here, we developed a protocol for extracting mixed perilymph-cerebrospinal fluid (P-CSF) from axolotl and provided the first proteomic and metabolomic characterization of this biological fluid. We identified 2,626 unique proteins and 173 high-confidence metabolites and quantified them across four time points of early limb regeneration. We demonstrated that limb amputation drives progressive shifts in P-CSF proteins, including an elevation of sarcomeric muscle proteins, regeneration-associated factors, and protease/extracellular matrix proteins. We observed shifts in metabolites involved in oxidative stress, polyunsaturated fatty acid oxidation, and histamine metabolism. Injury-comparison experiments revealed that the observed proteomic changes as a result of limb amputation are different than crush injury, denervation, or tail amputation. This study proposes axolotl P-CSF as a reservoir for limb amputation-associated systemic signaling and as a potential conduit of signals involved in limb regeneration.

systems biology↗

An evolutionarily conserved role for VEGF signaling in the expansion of non-vascular tissue during regeneration.

Salamanders are capable of regenerating whole limbs throughout life, a feat that is unmatched within tetrapods. Limb regeneration is dependent upon the formation of a blastema, which contains undifferentiated cells capable of giving rise to most cells of the regenerated limb. Innervation is required for regeneration, along with many signaling pathways, including FGF, BMP and Wnt, but the role of VEGF signaling during salamander limb regeneration is not well understood. Here we show that VEGF signaling is essential for limb regeneration and that blastema cells and limb fibroblasts display impaired proliferation in the absence of VEGF signaling. By performing analogous experiments in planaria, which lack vasculature, we show a potential evolutionarily conserved role for VEGF in the expansion of blastema tissues that is separable from angiogenesis. Moreover, loss of VEGF signaling reduces induction of EMT-like processes, suggesting VEGF signaling functions upstream of the expression of EMT transcription factors, including Snai2. These findings highlight potential roles for VEGF signaling during regeneration which may extend beyond typical findings related to angiogenesis.

developmental biology↗

Amputation Triggers Long-Range Epidermal Permeability Changes in Evolutionarily Distant Regenerative Organisms

Previous studies have reported that amputation invokes body-wide responses in regenerative organisms, but most have not examined the implications of these changes beyond the region of tissue regrowth. Specifically, long-range epidermal responses to amputation are largely uncharacterized, with research on amputation-induced epidermal responses in regenerative organisms traditionally being restricted to the wound site. Here, we investigate the effect of amputation on long-range epidermal permeability in two evolutionarily distant, regenerative organisms: axolotls and planarians. We find that amputation triggers a long-range increase in epidermal permeability in axolotls, accompanied by a long-range epidermal downregulation in MAPK signaling. Additionally, we provide functional evidence that pharmacologically inhibiting MAPK signaling in regenerating planarians increases long-range epidermal permeability. These findings advance our knowledge of body-wide changes due to amputation in regenerative organisms and warrant further study on whether epidermal permeability dysregulation in the context of amputation may lead to pathology in both regenerative and non-regenerative organisms. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/610385v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@81b022org.highwire.dtl.DTLVardef@52c2e9org.highwire.dtl.DTLVardef@17a5f93org.highwire.dtl.DTLVardef@118b8f6_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

An Interscholastic Network to Generate LexA Enhancer Trap Lines in Drosophila

Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the StonEx1 index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected KP element on chromosome III within the StanEx1 genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the NK7.1 locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in Drosophila for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.

genetics↗