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The preimplantation mouse embryo is a simple self-contained system, making it an excellent model to discover how mammalian cells function in real time and in vivo . Work over the last decade has revealed some key morphogenetic mechanisms that drive early development, yielding rudimentary instructions for the generation of a mammalian embryo. Here, we review the instructions revealed thus far, and then discuss remaining challenges to discover upstream factors controlling cell fate determination, test the role of mechanisms based on biological noise, and take advantage of recent technological developments to advance the spatial and temporal resolution of our current understanding. [ABSTRACT FROM AUTHOR]

During preimplantation development, cells of the mammalian embryo must resolve their shape and position to ensure the future viability of the fetus. These initial changes are established as the embryo expands from one to thirty-two cells, and a group of originally spherical cells is transformed into a more polarized structure with distinct cell geometries and lineages. Recent advances in the application of non-invasive imaging technologies have enabled the discovery of mechanisms regulating patterning of the early mammalian embryo. Here, we review recent findings revealing cell protrusions that trigger early changes in cell shape and embryo compaction, and how anisotropies in mechanical forces drive the first spatial segregation of cells in the embryo to form the pluripotent inner mass. [ABSTRACT FROM AUTHOR]

Highlights: [•] Glial cells play a critical role in maintenance of axonal integrity and function. [•] Diabetes mellitus modifies axon–glia interactions at nodal areas of PNS nerves. [•] Axonal energy metabolism and ion conductance are particularly affected. [•] These observations provide a basis for novel therapeutic and diagnostic approaches. [Copyright &y& Elsevier]

Delta (δ-) and epsilon (ε-) tubulin are lesser-known cousins of alpha (α-) and beta (β-) tubulin. They are likely to regulate centriole function in a broad range of species; however, their in vivo role and mechanism of action in mammals remain mysterious. In unicellular species and mammalian cell lines, mutations in δ- and ε-tubulin cause centriole destabilization and atypical mitosis and, in the most severe cases, cell death. Beyond the centriole, δ- and ε-tubulin localize to the manchette during murine spermatogenesis and interact with katanin-like 2 (KATNAL2), a protein with microtubule (MT)-severing properties, indicative of novel non-centriolar functions. Herein we summarize the current knowledge surrounding δ- and ε-tubulin, identify pathways for future research, and highlight how and why spermatogenesis and embryogenesis are ideal systems to define δ- and ε-tubulin function in vivo. Delta and epsilon tubulin are required for triplet microtubule stability in centrioles and basal bodies. Mutations in these tubulins result in compromised triplet microtubule structures, wherein the centriole loses its ability to facilitate efficient mitosis and the basal body has a reduced ability to form cilia. Delta and epsilon tubulin can interact with each other and are posited to interact with both alpha/beta tubulin and non-tubulin proteins. Delta and epsilon tubulin have shown localization to non-centriolar structures, indicative of a potential function outside the centriole. [ABSTRACT FROM AUTHOR]

Mammalian preimplantation embryogenesis depends on the spatio-temporal dynamics of the microtubule cytoskeleton to enable exceptionally fast changes in cell number, function, architecture, and fate. Microtubule organising centres (MTOCs), which coordinate the remodelling of microtubules, are therefore of fundamental significance during the first days of a new life. Despite its indispensable role during early mammalian embryogenesis, the origin of microtubule growth remains poorly understood. In this review, we summarise the most recent discoveries on microtubule organisation and function during early human embryogenesis and compare these to innovative studies conducted in alternative mammalian models. We emphasise the differences and analogies of centriole inheritance and their role during the first cleavage. Furthermore, we highlight the significance of non-centrosomal MTOCs for embryo viability and discuss the potential of novel in vitro models and light-inducible approaches towards unravelling microtubule formation in research and assisted reproductive technologies. • Centrosome dynamics during the first mitotic division influence the vulnerability of human embryos to aneuploidy. • Non-human mammalian embryogenesis models display plasticity in their use of non-centrosomal microtubule organising centres. • Comparative analysis of the available in vivo and in vitro models of mammalian embryogenesis. [ABSTRACT FROM AUTHOR]