Cortical development and asymmetric cell divisions

The development of the mammalian neocortex involves rounds of symmetric and asymmetric cell division of neural progenitors to fulfill needs of both self-renewal of progenitors and production of differentiated progenies such as neurons and glia. The machinery for asymmetric cell division is evolutionarily conserved and extensively used in organogeuesis and homeostasis of adult tissues. Here we summarize recent progress regarding cellular characteristics of different types of neural progenitors in mammals, highlighting how asymmetric cell division is utilized during cortical development.

Asymmetric cell division in plant development

Asymmetric cell division(ACD) is a fundamental process that generates new cell types during development in eukaryotic species.In plant development,post-embryonic organogenesis driven by ACD is universal and more important than in animals,in which organ pattern is preset during embryogenesis.Thus,plant development provides a powerful system to study molecular mechanisms underlying ACD.During the past decade,tremendous progress has been made in our understanding of the key components and mechanisms involved in this important process in plants.Here,we present an overview of how ACD is determined and regulated in multiple biological processes in plant development and compare their conservation and specificity among different model cell systems.We also summarize the molecular roles and mechanisms of the phytohormones in the regulation of plant ACD.Finally,we conclude with the overarching paradigms and principles that govern plant ACD and consider how new technologies can be exploited to fill the knowledge gaps and make new advances in the field.

In vivo imaging reveals mature Oligodendrocyte division in adult Zebrafish

Whether mature oligodendrocytes(mOLs)participate in remyelination has been disputed for several decades.Recently,some studies have shown that mOLs participate in remyelination by producing new sheaths.However,whether mOLs can produce new oligodendrocytes by asymmetric division has not been proven.Zebrafish is a perfect model to research remyelination compared to other species.In this study,optic nerve crushing did not induce local mOLs death.After optic nerve transplantation from olig2:eGFP fish to AB/WT fish,olig2^(+)cells from the donor settled and rewrapped axons in the recipient.After identifying these rewrapping olig2^(+)cells as mOLs at 3 months posttransplantation,in vivo imaging showed that olig2^(+)cells proliferated.Additionally,in vivo imaging of new olig2^(+)cell division from mOLs was also captured within the retina.Finally,fine visual function was renewed after the remyelination program was completed.In conclusion,our in vivo imaging results showed that new olig2^(+)cells were born from mOLs by asymmetric division in adult zebrafish,which highlights the role of mOLs in the progression of remyelination in the mammalian CNS.

Investigating the consequences of asymmetric endoplasmic reticulum inheritance in Saccharomyces cerevisiae under stress using a combination of single cell measurements and mathematical modelling

Adaptation allows organisms to maintain a constant internal environment,which is optimised for growth.The unfolded protein response(UPR)is an example of a feedback loop that maintains endoplasmic reticulum(ER)homeostasis,and is characteristic of how adaptation is often mediated by transcriptional networks.The more recent discovery of asymmetric division in maintaining ER homeostasis,however,is an example of how alternative non-transcriptional pathways can exist,but are overlooked by gold standard transcriptomic or proteomic population-based assays.In this study,we have used a combination of fluorescent reporters,flow cytometry and mathematical modelling to explore the relative roles of asymmetric cell division and the UPR in maintaining ER homeostasis.Under low ER stress,asymmetric division leaves daughter cells with an ER deficiency,necessitating activation of the UPR and prolonged cell cycle during which they can recover ER functionality before growth.Mathematical analysis of and simulation results from our mathematical model reinforce the experimental observations that low ER stress primarily impacts the growth rate of the daughter cells.These results demonstrate the interplay between homeostatic pathways and the importance of exploring sub-population dynamics to understand population adaptation to quantitatively different stresses.

Liquid-liquid phase separation in biology: mechanisms,physiological functions and human diseases

Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecular mechanisms underlying the dynamics of membrane-bound organelles, such as their fusion and fission, vesicle-mediated trafficking and membrane contactmediated inter-organelle interactions, have been extensively characterized. However, the molecular details of the assembly and functions of membraneless compartments remain elusive. Mounting evidence has emerged recently that a large number of membraneless compartments, collectively called biomacromolecular condensates, are assembled via liquid-liquid phase separation(LLPS). Phase-separated condensates participate in various biological activities, including higher-order chromatin organization,gene expression, triage of misfolded or unwanted proteins for autophagic degradation, assembly of signaling clusters and actin-and microtubule-based cytoskeletal networks, asymmetric segregations of cell fate determinants and formation of pre-and post-synaptic density signaling assemblies. Biomacromolecular condensates can transition into different material states such as gel-like structures and solid aggregates. The material properties of condensates are crucial for fulfilment of their distinct functions, such as biochemical reaction centers, signaling hubs and supporting architectures. Cells have evolved multiple mechanisms to ensure that biomacromolecular condensates are assembled and disassembled in a tightly controlled manner. Aberrant phase separation and transition are causatively associated with a variety of human diseases such as neurodegenerative diseases and cancers. This review summarizes recent major progress in elucidating the roles of LLPS in various biological pathways and diseases.

Regulation of muscle stem cell fate

Skeletal muscle plays a critical role in human health.Muscle stem cells(MuSCs)serve as the major cell type contribut-ing to muscle regeneration by directly differentiating to mature muscle cells.MuSCs usually remain quiescent with occasionally self-renewal and are activated to enter cell cycle for proliferation followed by differentiation upon muscle injury or under pathological conditions.The quiescence maintenance,activation,proliferation,and differentiation of MuSCs are tightly regulated.The MuSC cell-intrinsic regulatory network and the microenvironments work coordi-nately to orchestrate the fate transition of MuSCs.The heterogeneity of MuSCs further complicates the regulation of MuSCs.This review briefly summarizes the current progress on the heterogeneity of MuSCs and the microenviron-ments,epigenetic,and transcription regulations of MuSCs.

Establishing cell polarity by the Lgl family proteins

The lethal giant larvae(lgl)gene was first identified more than 30 years ago in Drosophila and characterized as a tumor suppressor gene.Studies in budding yeast,flies and mammals all indicate that the evolutionarily conserved Lgl family proteins play an important role in cell polarity.Sro7/77,the yeast Lgl homologues,are important for the establishment and reinforcement of cell polarity through their localized interaction and kinetic activation of the post-Golgi secretion machinery.As for higher eukaryotes,both in epithelial polarity and asymmetric cell division,the role of Lgl protein is deployed by localizing proteins to the membrane in a polarized fashion.In addition,Lgl is transiently required during the establishment phase of polarity,implicating that Lgl functions at strategic time points for proliferation control.Studies in cancer biology provide direct connections between malfunction of Lgl and formation,progression and metastasis of various cancers.Here,we review recent advances in the field,focusing on the function of the Lgl family in cellular polarization.

Chromophore-assisted laser inactivation in neural development

Chromophore-assisted laser inactivation（CALI） is a technique that uses photochemically-generated reactive oxygen species to acutely inactivate target proteins in living cells.Neural development includes highly dynamic cellular processes such as asymmetric cell division,migration,axon and dendrite outgrowth and synaptogenesis.Although many key molecules of neural development have been identified since the past decades,their spatiotemporal contributions to these cellular events are not well understood.CALI provides an appealing tool for elucidating the precise functions of these molecules during neural development.In this review,we summarize the principles of CALI,a recent microscopic setup to perform CALI experiments,and the application of CALI to the study of growth-cone motility and neuroblast asymmetric division.

Cytoskeleton and Early Development in Fucoid Algae

Cell polarization and asymmetric cell divisions play important roles during development in many multicellular eukaryotes. Fucoid algae have a long history as models for studying early developmental processes, probably because of the ease with which zygotes can be observed and manipulated in the laboratory. This review discusses cell polarization and asymmetric cell divisions in fucoid algal zygotes with an emphasis on the roles played by the cytoskeleton.