- Mitochondrial Function and Pathology
- Zebrafish Biomedical Research Applications
- Adipose Tissue and Metabolism
- Developmental Biology and Gene Regulation
- Physiological and biochemical adaptations
- Cancer, Hypoxia, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Congenital heart defects research
- Tendon Structure and Treatment
- Muscle Physiology and Disorders
- Kruppel-like factors research
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Barrier Structure and Function Studies
- Angiogenesis and VEGF in Cancer
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- ATP Synthase and ATPases Research
- Erythrocyte Function and Pathophysiology
- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
University of Calgary
2018-2024
Alberta Children's Hospital
2018-2024
Alberta Children's Hospital Research Institute
2023
Queen's University
2010-2015
Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population blood vessel associated cells. In contrast pericytes, emerge early during development, express extracellular matrix (ECM) genes col1a2 col5a1 , display...
Development of a functional musculoskeletal system requires coordinated generation muscles, bones, and tendons. However, how axial tendon cells (tenocytes) are generated during embryo development is still poorly understood. Here, we show that tenocytes arise from the sclerotome in zebrafish. In contrast to mouse chick, zebrafish consists two separate domains: ventral domain previously undescribed dorsal domain. While dispensable for induction, Hedgehog (Hh) signaling required migration...
Many fish species respond to low temperature by inducing mitochondrial biogenesis, reflected in an increase activity of the enzyme cytochrome c oxidase (COX). COX is composed 13 subunits, three encoded (mt)DNA and 10 nuclear genes. We used real-time PCR measure mRNA levels for nuclear-encoded genes that are highly expressed muscle. measured white muscle minnow species, each at two temperatures: zebrafish (Danio rerio) acclimated 11 30°C, goldfish (Carassius auratus) 4 35°C, northern redbelly...
Vertebrates possess two paralogs of cytochrome c oxidase (COX) subunit 4: a ubiquitous COX4-1 and hypoxia-linked COX4-2. Mammalian COX4-2 is thought to have role in relation fine-tuning metabolism low oxygen levels, conferred through both structural differences the protein structure regulatory gene. We sought elucidate pervasiveness this feature across vertebrates. The ratio COX4-2/4-1 mRNA generally mammals, but was higher fish reptiles, particularly turtles. gene appeared unresponsive...
Vertebrate mitochondrial cytochrome c oxidase (COX) possesses 10 nuclear-encoded subunits. Six subunits have paralogs in mammals, but the origins and distribution of isoforms among vertebrates not been analyzed. We used Bayesian phylogenetic analysis to interpret each subunit, inferring roles gene genome duplications. The paralogous ancestries five genes were identical throughout major vertebrate taxa: no COX6c COX7c, two COX4 COX6a, three COX7a. Two had an extra copy teleosts (COX5a,...
Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to brain. The genetic pathways guiding undifferentiated cells into mature not well understood. We show here pericyte precursor populations from both neural crest head mesoderm zebrafish express transcription factor nkx3 . 1 develop brain pericytes. identify gene signature these precursors an -, foxf2a cxcl12b -expressing population is present around...
Muscle stem cells hold a great therapeutic potential in regenerating damaged muscles. However, the vivo behavior of muscle during growth and regeneration is still poorly understood. Using zebrafish as model, we describe dynamics function embryonic progenitor (MPCs) dermomyotome. These are located superficial layer external to fibers express many extracellular matrix (ECM) genes, including collagen type 1 α2 (col1a2). Utilizing new col1a2 transgenic line, show that col1a2+ MPCs display...
ABSTRACT Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population blood vessel associated cells. In contrast pericytes, emerge early during development, express extracellular matrix (ECM) genes col1a2 col5a1 ,...
Modification of mitochondrial content demands the synthesis hundreds proteins encoded by nuclear and genomes. The responsibility for coordination this process falls to nuclear-encoded master regulators transcription. DNA-binding coactivators integrate information from energy-sensing pathways hormones alter gene expression. In mammals, signaling cascade biogenesis can be described as follows: hormonal signals energetic are sensed protein-modifying enzymes that in turn regulate...
Do the transcriptional mechanisms that control an individual's mitochondrial content, PGC1α (peroxisome proliferator-activated receptor γ coactivator-1α) and NRF1 (nuclear respiratory factor-1), also cause differences between species? We explored determinants of cytochrome c oxidase (COX) activities in muscles from 12 rodents differing 1,000-fold mass. Hindlimb differed scaling patterns isometric (soleus, gastrocnemius) to allometric (tibialis anterior, coefficient = -0.16). Consideration...
The sclerotome is an embryonic structure that gives rise to various supportive tissues, including the axial skeleton and connective tissues. Despite its significance, mechanisms underlying induction diversification during development remain poorly understood. Sclerotome progenitors exhibit transient bmp4 expression active response BMP signaling. Using gain- loss-of-function tools, we demonstrate signaling both necessary sufficient for induction. Furthermore, through mosaic of a...
In vertebrates, the sclerotome is a transient embryonic structure that gives rise to various tissue support cells, including fibroblasts. However, how fibroblast precursors are guided diverse tissues remain poorly understood. Using zebrafish, our lab has previously shown sclerotome-derived cells undergo extensive migration generate distinct fibroblasts subtypes, tenocytes along myotendinous junction and fin mesenchymal in fold. Interestingly, pan-fibroblast gene platelet-derived growth...
Paired locomotion appendages are hypothesized to have redeployed the developmental program of median appendages, such as dorsal and anal fins. Compared with paired fins, limbs, remain surprisingly understudied. Here, we report that a dominant zebrafish mutant, smoothback(smb), fails develop fin. Moreover, fin is reduced along antero-posterior axis, spine defects develop. Mechanistically, smb caused by an insertion sox10:Gal4VP16transgenic construct into non-coding region. The first step in...
ABSTRACT Muscle stem cells hold a great therapeutic potential in regenerating damaged muscles. However, the vivo behavior of muscle during growth and regeneration is still poorly understood. Using zebrafish as model, we describe dynamics function dermomyotome cells, population embryonic progenitor cells. Dermomyotome are located superficial layer external to fibers express many extracellular matrix (ECM) genes including col1a2 . Utilizing new transgenic line, show that display ramified...
Are the transcriptional mechanisms that control mitochondrial content in an individual ‐NRF1 and PGC1alpha (PGC1)‐ also responsible for interspecies differences? We explored origins of allometric scaling cytochrome oxidase (COX) activities muscles from 12 rodents differing 1000‐fold mass. Muscle COX patterns ranged isometric (soleus) to (tibialis anterior). Consideration myonuclear domain reduced differences between muscles, but not differences. In tibialis anterior, there was no significant...
Abstract Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to brain. The genetic pathways guiding undifferentiated cells into mature not well understood. We show here pericyte precursor populations from both neural crest head mesoderm zebrafish express transcription factor nkx3.1 develop brain pericytes. identify gene signature these precursors, an nkx3.1, foxf2a , cxcl12b -expressing population is...
Among the mechanisms that fine‐tune cytochrome c oxidase (COX) levels/activities is an oxygen‐dependent switch of paralogs for subunit 4. COX4‐1 constitutively expressed in most tissues; COX4‐2 predominates brain and lung induced by hypoxia other tissues. Though there considerable evidence this isoform has advantages COX regulation under energetic stress, evolutionary origins adaptation are unclear. All vertebrates possess single gene copies both orthologs, though birds lack a functional...
ABSTRACT Fibroblasts play an important role in maintaining tissue integrity by secreting components of the extracellular matrix and initiating response to injury. Although function fibroblasts has been extensively studied adults, embryonic origin diversification different fibroblast subtypes during development remain largely unexplored. Using zebrafish as a model, we show that sclerotome, sub-compartment somite, is source multiple including tenocytes (tendon fibroblasts), blood vessel...
ABSTRACT During neural development, progenitor cells generate different types of neurons in specific time windows. Despite the characterisation many transcription factor networks involved these differentiation events, mechanism behind their temporal regulation is poorly understood. To address this question, we studied simple lateral floor plate (LFP) domain zebrafish spinal cord. LFP progenitors sequentially early-born Kolmer-Agduhr” (KA”) interneurons and late-born V3 interneurons. Analysis...