Top 5 Biorxiv Papers Today
in Developmental Biology
Desingu Ayyappa Raja,
Rajesh S Gokhale,
vivek T natarajan
In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical for both development and regeneration. While the fate-commitment events have distinct transcriptional footprints, fate-biasing is often transitory and metastable, and is thought to be moulded by epigenetic programs. Hence molecular basis of specification is difficult to define. In this study, we establish a role of a histone variant H2a.z.2 in specification of melanocyte lineage from multipotent neural crest cells. Silencing of H2a.z.2 reduces the number of melanocyte precursors in developing zebrafish embryos, and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of key melanocyte determinant Mitf, and enhances its induction. CRISPR-Cas9 based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby our study establishes a histone based specification code upstream to the core gene regulatory network...
Histone code dictates fate biasing of neural crest cells to melanocyte lineage https://t.co/GzaVC8fjzN #bioRxiv
Total Words: 12119
Unqiue Words: 3670
To produce a directional flow, ciliated epithelia display a uniform orientation of ciliary beating. Oriented beating requires planar cell polarity (PCP), which leads to planar orientation and asymmetric positioning of the ciliary basal body (BB) along the polarity axis. We took advantage of the polarized mono-ciliated epithelium of the embryonic zebrafish floor plate (FP) to investigate by live-imaging the dynamics and mechanisms of BB polarization. We showed that BBs, although bearing a cilium, were highly motile along the polarity axis, contacting either the anterior or posterior membranes, exclusively at the level of apical junctions positive for Par3. Par3 was posteriorly enriched before BB posterior positioning and FP polarization was disrupted upon Par3 overexpression. In the PCP mutant Vangl2, BBs showed poorly oriented movements correlated with Par3 mislocalization. Our data lead us to propose a conserved function for Par3 in controlling BB asymmetric positioning downstream of the PCP pathway.
PLANAR POLARIZATION OF CILIA IN THE ZEBRAFISH FLOOR PLATE INVOLVES Par3-MEDIATED POSTERIOR LOCALIZATION OF HIGHLY MOTILE BASAL BODIES. https://t.co/CajU6EiPrh #bioRxiv
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Total Words: 13339
Unqiue Words: 3155
Gene expression is in part a stochastic process, which is at odds with the need for precise expression levels in biological processes such as embryonic development. To study the tension between precision and stochasticity of gene expression during development, we quantified expression variability of single embryo transcriptomes throughout fly Drosophila melanogaster embryogenesis, from 150 samples over eight developmental stages. We found that expression variability follows an hourglass pattern, with lower variability at extended germband, the phylotypic stage. We explain this pattern by stronger histone modification mediated transcriptional noise control at this stage. In addition, we propose that histone modifications contribute to mutational robustness in regulatory elements, and thus to conserved expression levels. These results provide insight into the role of robustness in the phenotypic and genetic patterns of evolutionary conservation in animal development.
An hourglass pattern of inter-embryo gene expression variability and of histone regulation in fly embryogenesis https://t.co/QJkwslTbn2 #bioRxiv
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H19 and Gtl2 are paternal imprinted genes that are pivotal for prenatal embryonic development. Meanwhile, mouse nongrowing oocytes and sperm- or oocyte-originated haploid embryonic stem cells (haESCs) carrying both H19 and IG-DMR (differentially DNA-methylated region) deletions (DKO) that partially mimic paternal imprinting of H19-Igf2 and Dlk1-Dio3 can be employed as sperm replacement to efficiently support full-term embryonic development. However, how H19-DMR and IG-DMR act together to regulate embryonic development is still largely unknown. Here, using androgenetic haESC (AG-haESC)-mediated semi-cloned (SC) technology, we showed that paternal H19-DMR and IG-DMR are not essential for pre-implantation development of SC embryos generated through injection of AG-haESCs into oocytes. H19-DMR plays critical roles before 12.5 days of gestation while IG-DMR is essential for late-gestation of SC embryos. Interestingly, we found that combined deletions of H19 and H19-DMR can further improve the efficiency of normal development of SC...
Temporal regulation of prenatal embryonic development by paternal imprinted loci https://t.co/nWgtOvHKYe #bioRxiv
Total Words: 12931
Unqiue Words: 3104
Glutamate cysteine ligase catalytic subunit (Gclc) is the catalytic subunit for the glutamate-cysteine ligase (Gcl) enzyme. Gcl catalyzes the rate limiting step in glutathione (GSH) synthesis. Gclc is highly expressed in the developing eye. To define the regulatory role of Gclc in eye development, we developed a novel, Le-Cre transgene-driven, Gclc knockout mouse model. Gclcf/f/Le-CreTg/- mice present with deformation of the retina, cornea, iris, and lens, consistent with a microphthalmia phenotype. Controlling for the microphthalmia phenotype of Gclcwt/wt/Le-CreTg/- mice revealed that Gclcf/f/Le-CreTg/- mice have a more severe microphthalmia phenotype. Thus, the loss of Gclc expression exacerbates the microphthalmia phenotype in Le-Cre mice. Gclcf/f/Le-CreTg/- eyes present with reduced retinal and lens epithelium proliferation and increased lens cell death. Imaging mass spectrometry of ocular tissues revealed changes in the intensity and distribution of several lipid species and proteins in the retina and corneas of...
Gclc deletion in surface-ectoderm tissues induces microphthalmia https://t.co/XbyOts4QN0 #bioRxiv
Total Words: 10835
Unqiue Words: 3523
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