Satellite cell division and fiber hypertrophy alternate with new fiber formation during indeterminate muscle growth in juvenile Lake Sturgeon (Acipenser fulvescens)

Age-dependent changes in muscle fiber size, myonuclear domain volume, fiber-end-terminal configuration, fiber and fish growth, and stem cell or satellite cell (SC) number and proliferation were investigated in developing lake sturgeon (Acipenser fulvescens Rafinesque, 1817) to characterize indeterminate muscle growth during early life. We hypothesized that up to 29 months post hatch (MPH), SC numbers and mitotic activity, the mitotic cycle duration of SCs, fiber morphology, and the volume of cytoplasmic domains around fiber nuclei would change during periods of fiber hypertrophy and hyperplasia. Single-fiber cultures were used in pulse-chase studies of SC division and the Pax7+ SC population. The number of SCs per fiber increased until 17 MPH, peaking as a proportion of fiber nuclei at 3 and 17 MPH. SC cycle time decreased in duration with age after peaks at 3 and 5 MPH. Domain volume was high at 1 and 29 MPH and low from 2 to 6 MPH. Fibers with uniformly tapered ends were most frequent at 4 MPH. Results suggest 3 and 6–17 MPH as intervals for both SC proliferation and fiber hypertrophy, and that fiber growth alternated with new fiber formation (termed fiber hyperplasia) from 4 to 5 MPH and from 17 to 29 MPH. These patterns of cellular dynamics in lake sturgeon muscle growth advance our understanding of indeterminate growth.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Climbing Waterfalls: How Metabolism and Behavior Impact Locomotor Performance of Tropical Climbing Gobies on Reunion Island

International audienceThe life cycle of gobies of the Sicydiinae subfamily depends on climbing waterfalls. Two sympatric sicydiines species from Reunion Island, Sicyopterus lagocephalus (SIL) and Cotylopus acutipinnis (COA), employ different climbing modes. SIL uses a steady “inching” mode interrupted by short rest periods, whereas COA exhibits short “power-burst” undulatory movements punctuated by longer rest periods. Consequently, we explored the relationship between climbing performance and metabolic activity in these two species. We demonstrated that the two climbing modes are supported by different ecophysiological profiles that promote the interspecific variability of locomotor performance. More specifically, SIL performed better than COA during a climbing experiment because of its inching climbing mode, supported by a generally greater metabolic capacity and a higher potential for oxidative metabolism. Interestingly, we did not detect any difference in metabolic fuel storage and lactate production during climbing in either species, suggesting that these species can maintain fuel reserves and limit lactate accumulation through extensive rest times. Overall, this study provides new insights into the ecophysiology of these two emblematic species and suggests that the better climbing capacity of SIL is supported by its muscular metabolic capacity

Climbing Waterfalls: How Metabolism and Behavior Impact Locomotor Performance of Tropical Climbing Gobies on Reunion Island

The life cycle of gobies of the Sicydiinae subfamily depends on climbing waterfalls. Two sympatric sicydiines species from Reunion Island, Sicyopterus lagocephalus (SIL) and Cotylopus acutipinnis (COA), employ different climbing modes. SIL uses a steady “inching” mode interrupted by short rest periods, whereas COA exhibits short “power-burst” undulatory movements punctuated by longer rest periods. Consequently, we explored the relationship between climbing performance and metabolic activity in these two species. We demonstrated that the two climbing modes are supported by different ecophysiological profiles that promote the interspecific variability of locomotor performance. More specifically, SIL performed better than COA during a climbing experiment because of its inching climbing mode, supported by a generally greater metabolic capacity and a higher potential for oxidative metabolism. Interestingly, we did not detect any difference in metabolic fuel storage and lactate production during climbing in either species, suggesting that these species can maintain fuel reserves and limit lactate accumulation through extensive rest times. Overall, this study provides new insights into the ecophysiology of these two emblematic species and suggests that the better climbing capacity of SIL is supported by its muscular metabolic capacity

Myeloid translocation genes differentially regulate colorectal cancer programs

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1 −/− mice have progressive depletion of all intestinal secretory cells, and Mtg16 −/− mice have a decrease in goblet cells. Furthermore, both Mtgr1 −/− and Mtg16 −/− mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc 1638/+ -dependent intestinal tumorigenesis. Mtgr1 −/− mice, but not Mtg16 −/− mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of ChIP-seq datasets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1 −/− tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context dependent effect on intestinal tumorigenesis

MTG16 is a tumor suppressor in colitis-associated carcinoma

MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16 –/– mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis. MTG16 was downregulated at the protein and RNA levels in patients with inflammatory bowel disease and in those with colitis-associated carcinoma. Mtg16 –/– mice subjected to inflammatory carcinogenesis modeling exhibited worse colitis and increased tumor multiplicity and size. Loss of MTG16 also increased severity of dysplasia, apoptosis, proliferation, DNA damage, and WNT signaling. Moreover, transplantation of WT marrow into Mtg16 –/– mice failed to rescue the Mtg16 –/– protumorigenic phenotypes, indicating an epithelium-specific role for MTG16. While MTG dysfunction is widely appreciated in hematopoietic malignancies, the role of this gene family in epithelial homeostasis, and in colon cancer, was unrealized. This report identifies MTG16 as an important modulator of colitis and tumor development in inflammatory carcinogenesis. Myeloid translocation gene 16 is a modulator of colitis and tumor development in colitis-associated carcinoma

MTG16 contributes to colonic epithelial integrity in experimental colitis

OBJECTIVE: The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8(−/−) and Mtgr1(−/−) mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. METHODS: Baseline and stress induced colonic phenotypes were examined in Mtg16(−/−) mice. To unmask phenotypes, we treated Mtg16(−/−) mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. RESULTS: Mtg16(−/−) mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16(−/−) mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1(+), F4/80(+), CD11c(+) and MHCII(+); CD11c(+)) and Th1 adaptive (CD4) immune cells in Mtg16(−/−) colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16(−/−) colons. Compared with wild-type mice, Mtg16(−/−) mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wildtype marrow into Mtg16(−/−) recipients did not rescue the Mtg16(−/−) injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16(−/−) mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16(−/−) mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. CONCLUSIONS: These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury