bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/261685

Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation.

Sharma, A.·Agarwal, M.·Kumar, A.·Kumar, P.·Saini, M.·Kardon, G.·Mathew, S.
View original source ↗Export metadata ↓

Abstract

Myosin heavy chains (MyHCs) are contractile proteins that are part of the thick filaments of the functional unit of the skeletal muscle, the sarcomere. In addition to MyHCs that are part of the adult muscle contractile network, two MyHCs - MyHC-embryonic and -perinatal are expressed during muscle development and are only transiently expressed in the adult during regeneration. The functions performed by these MyHCs has been a long-standing question and using a targeted mouse allele, we have characterized the role of MyHC-embryonic. Analysis of loss-of-function mice reveals that lack of MyHC-embryonic leads to mis-regulation of other MyHCs, alterations in fiber size, fiber number and fiber type at neonatal stages. We also find that loss of MyHC-embryonic leads to mis-regulation of genes involved in muscle differentiation. A broad theme from these studies is that loss of MyHC-embryonic has distinct effects on different muscles, possibly reflecting the unique fiber type composition of different muscles. Most significantly, our results indicate that MyHC-embryonic is required during embryonic and fetal myogenesis to regulate myogenic progenitor and myoblast differentiation in a non-cell autonomous manner via Mitogen Activated Protein Kinase (MAPKinase) and Fibroblast Growth Factor (FGF) signaling. Thus, our results signify that MyHC-embryonic is a key regulator of myogenic differentiation during embryonic, fetal and neonatal myogenesis.

Source connections

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sharma, A., Agarwal, M., Kumar, A., Kumar, P., Saini, M., Kardon, G., Mathew, S.. 2018-02-07. Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation.. https://doi.org/10.1101/261685

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Coding region changes in the Hippo pathway component YAP1 contribute to body size differences among mammalian species

Animal species differ dramatically in their overall size, yet the mechanisms underlying these differences are poorly understood. The Hippo pathway, first discovered in Drosophila, and widely conserved in mammals, regulates the nuclear levels of YAP1, a transcriptional co-activator that enhances the expression of growth-promoting genes. While experimental manipulations of this pathway elicit dramatic effects on tissue growth and organ size, it is not known whether, and to what extent, evolutionary divergence of this pathway has contributed to size differences across animals. Here we show that although YAP1 protein sequence is highly conserved between diverse mammals such as humans, elephants and blue whales, it diverges considerably among rodent species. While the human YAP1 protein is very similar to that of the largest rodent, the capybara Hydrochoerus hydrochaeris, those of smaller rodents such as the mouse Mus musculus and the vole Microtus oregoni show considerable divergence. An increased ratio of non-synonymous versus synonymous substitutions (dN/dS) in clades of small rodents compared to the background is indicative of relaxed constraint in these lineages, suggesting relative positive selection. When expressed in the developing Drosophila wing, capybara YAP1 was more potent at promoting growth than that of the mouse or vole. Following transfection into mammalian cells, capybara YAP1 is more effective at promoting expression of a reporter gene than either mouse or vole YAP1. Thus, by combining computational and experimental approaches, we show that evolutionarily divergent coding-region changes in YAP1 have likely contributed to the evolution of smaller body size in clades of rodents.

developmental biology↗
bioRxiv2026

Molecular dissection of the ChAHP complex subunits Adnp and Chd4 reveals common and divergent functions in retinal development

Epigenetic remodelling is thought to regulate the progression of competence states in neural progenitor cells. Here, we examined the functions of the ChAHP chromatin remodelling complex during retinal development. ChAHP consists of the ATP-dependent nucleosome remodeller CHD4, the zinc finger and homeodomain transcription factor ADNP, and the HP1 heterochromatin proteins (Cbx1/3/5). Notably, both CHD4 and ADNP are genetically associated with neurodevelopmental disorders (NDDs), but ChAHP functions in neural development are not fully understood. In the retina, we found that both ADNP and CHD4 proteins were co-expressed ubiquitously in each cell type throughout development, and the two proteins formed a complex in vivo. Next, we generated retina-specific conditional knockouts (cKOs) to both Adnp and Chd4 using the Chx10-Cre driver. We observed phenotypic correspondence and divergence. Developmentally, we observed elevated cell death in both Adnp and Chd4 cKOs, but Adnp cKOs also exhibited deficits in progenitor numbers and proliferation. As a result, mature Adnp cKOs were hypoplastic with reductions in each cell type. We previously described a more complex phenotype in Chd4 cKOs, where cell fates were imbalanced and progenitor proliferation was prolonged, but these features were absent from the Adnp cKO. To understand how ChAHP regulates gene expression, we compared Adnp and Chd4 cKOs via scRNA-seq, which revealed common transcriptional signatures. However, Chd4 cKOs exhibited more severe effects on gene expression in line with its stronger effects on cell fate. We then performed cut&run-seq, which suggested that Adnp and Chd4 are recruited to the same genomic loci - many of which are also occupied by the Ctcf transcription factor. Taken together, our data suggest that ChAHP regulates retinal growth, but that CHD4 has additional ChAHP-independent functions in regulating progenitor fate decisions. These findings point to the idea that during neurogenesis, some brain regions may have greater dependence on ChAHP, and therefore greater vulnerability to genetic mutation.

developmental biology↗
bioRxiv2026

Fertilization offsets the maternal age effect on mouse oocytes provided the oviduct is not itself aged

Advanced maternal age compromises oocyte quality, and it is widely assumed that these deficits are transmitted to embryos. However, because most studies rely on in vivo conception, it has been difficult to separate the effects of oocyte aging from those of an aged fertilization environment. In aging mice, we observed that the fraction of ovulated oocytes forming implantation sites after in vivo conception fell ~3.7-fold, raising the question of whether this was due to reduced fertilization, reduced embryo quality or reduced support from the aged reproductive tract. Therefore we fertilized oocytes of aged and young mice in vitro with a shared young-donor sperm preparation, holding the fertilization environment constant and removing paternal variability. Hallmarks of maternal age were largely offset following fertilization in vitro: aged oocytes produced blastocysts at rates comparable to young controls, with altered - but not deficient - cell-lineage composition and no detectable impairment in development to term (E18.5) after transfer to young oviducts. Proteomic analysis revealed that, unlike the transcriptomic signature, the proteomic age signature of oocytes was not faithfully propagated to the blastocyst: for a subset of proteins, particularly those depleted in aged oocytes, the direction of the age effect reversed between oocyte and blastocyst. Comparison with parthenogenetically activated oocytes showed this divergence to be fertilization-dependent, implicating fertilization - rather than mere embryonic cleavage - as the driver of proteomic change. Stable-isotope labelling in live embryos showed that blastocysts from aged, fertilized oocytes both synthesized more new protein and retained less maternal protein than young counterparts; neither effect was detectable after parthenogenesis. Puromycin labelling, by contrast, showed a maternal-age-associated rise in bulk synthesis regardless of route. Together, these results indicate that the maternal-age effect on the oocyte proteome is labile rather than fixed and can be offset by fertilization itself, provided the maternal environment is not itself aged.

developmental biology↗