Jumeaux, a novel Drosophila winged-helix family protein, is required for generating asymmetric sibling neuronal cell fates

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3325-3335 ◽  
Author(s):  
P.Y. Cheah ◽  
W. Chia ◽  
X. Yang
Keyword(s):  
Cell Division ◽  
Neuronal Cell ◽  
Great Majority ◽  
Cell Fates ◽  
Winged Helix ◽  
Asymmetric Cell Divisions ◽  
Preferential Segregation ◽  
Family Protein ◽  
Embryonic Cns ◽  
Ganglion Mother Cell

The great majority of neurons in the Drosophila embryonic CNS are generated through two successive asymmetric cell divisions; neuroblasts (NBs) divide to produce another NB and a smaller ganglion mother cell (GMC); GMCs divide to generate two sibling neurons which can adopt distinct identities. During the division of the first born GMC from the NB4-2 lineage, GMC4-2a, Inscuteable (Insc) is localised to the apical cortex, Pon/Numb is localised to the basal cortex and two daughters with distinct identities, the RP2 motoneuron and its sibling RP2sib, are born. Resolution of distinct sibling neuronal fates requires correct apical localisation of Insc to facilitate the asymmetric localisation and preferential segregation of Pon/Numb to the basal daughter destined to become RP2. Here we report that jumeaux (jumu), which encodes a new member of the winged-helix family of transcription factors, is required to mediate the asymmetric localisation and segregation of Pon/Numb but is dispensable for Insc apical localisation during the GMC4-2a cell division. In jumu mutants GMC4-2a Pon/Numb asymmetric localisation is defective and both daughter neurons can adopt the RP2 identity. Jumu protein shows nuclear localisation and within the NB4-2 lineage is first detected only after the first neuroblast cell division, in GMC4-2a. Our results suggest that in addition to the correct formation of an apical complex, transcription mediated by Jumu is also necessary to facilitate the correct asymmetric localisation and segregation of Pon/Numb.

Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts

Development ◽  
2002 ◽  
Vol 129 (20) ◽  
pp. 4843-4853 ◽  
Author(s):  
Qin Shen ◽  
Weimin Zhong ◽  
Yuh Nung Jan ◽  
Sally Temple
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Progenitor Cells ◽  
Cortical Development ◽  
Cell Fates ◽  
Unequal Distribution ◽  
Asymmetric Cell Divisions ◽  
Neural Lineage ◽  
Cell Divisions ◽  
Β Tubulin

Stem cells and neuroblasts derived from mouse embryos undergo repeated asymmetric cell divisions, generating neural lineage trees similar to those of invertebrates. In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates. We investigated whether a mouse homologue m-numb had a similar role during mouse cortical development. Progenitor cells isolated from the embryonic mouse cortex were followed as they underwent their next cell division in vitro. Numb distribution was predominantly asymmetric during asymmetric cell divisions yielding a β-tubulin III− progenitor and a β-tubulin III+ neuronal cell (P/N divisions) and predominantly symmetric during divisions producing two neurons (N/N divisions). Cells from the numb knockout mouse underwent significantly fewer asymmetric P/N divisions compared to wild type, indicating a causal role for Numb. When progenitor cells derived from early (E10) cortex undergo P/N divisions, both daughters express the progenitor marker Nestin, indicating their immature state, and Numb segregates into the P or N daughter with similar frequency. In contrast, when progenitor cells derived from later E13 cortex (during active neurogenesis in vivo) undergo P/N divisions they produce a Nestin+ progenitor and a Nestin– neuronal daughter, and Numb segregates preferentially into the neuronal daughter. Thus during mouse cortical neurogenesis, as in Drosophila neurogenesis, asymmetric segregation of Numb could inhibit Notch activity in one daughter to induce neuronal differentiation. At terminal divisions generating two neurons, Numb was symmetrically distributed in approximately 80% of pairs and asymmetrically in 20%. We found a significant association between Numb distribution and morphology: most sisters of neuron pairs with symmetric Numb were similar and most with asymmetric Numb were different. Developing cortical neurons with Numb had longer processes than those without. Numb is expressed by neuroblasts and stem cells and can be asymmetrically segregated by both. These data indicate Numb has an important role in generating asymmetric cell divisions and diverse cell fates during mouse cortical development.

scholarly journals The Caenorhabditis elegans LIN-26 protein is required to specify and/or maintain all non-neuronal ectodermal cell fates

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2579-2588 ◽  
Author(s):  
M. Labouesse ◽  
E. Hartwieg ◽  
H.R. Horvitz
Keyword(s):  
Expression Patterns ◽  
Neuronal Cell ◽  
Loss Of Function ◽  
Cell Fates ◽  
Asymmetric Cell Divisions ◽  
Zinc Finger Transcription Factor ◽  
C Elegans ◽  
Cell Divisions ◽  
Mutant Phenotypes ◽  
Cell Expression

The C. elegans gene lin-26, which encodes a presumptive zinc-finger transcription factor, is required for hypodermal cells to acquire their proper fates. Here we show that lin-26 is expressed not only in all hypodermal cells but also in all glial-like cells. During asymmetric cell divisions that generate a neuronal cell and a non-neuronal cell, LIN-26 protein is symmetrically segregated and then lost from the neuronal cell. Expression in glial-like cells (socket and sheath cells) is biologically important, as some of these neuronal support cells die or seem sometimes to be transformed to neuron-like cells in embryos homozygous for strong loss-of-function mutations. In addition, most of these glial-like cells are structurally and functionally defective in animals carrying the weak loss-of-function mutation lin-26(n156). lin-26 mutant phenotypes and expression patterns together suggest that lin-26 is required to specify and/or maintain the fates not only of hypodermal cells but also of all other non-neuronal ectodermal cells in C. elegans. We speculate that lin-26 acts by repressing the expression of neuronal-specific genes in non-neuronal cells.

discordia mutations specifically misorient asymmetric cell divisions during development of the maize leaf epidermis

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4623-4633 ◽  
Author(s):  
K. Gallagher ◽  
L.G. Smith
Keyword(s):  
Cell Division ◽  
Preprophase Band ◽  
Cytochalasin D ◽  
Leaf Epidermis ◽  
Asymmetric Cell Divisions ◽  
Maize Leaf ◽  
Cell Divisions ◽  
Cytoskeletal Structure ◽  
Dividing Cells ◽  
Preprophase Bands

In plant cells, cytokinesis depends on a cytoskeletal structure called a phragmoplast, which directs the formation of a new cell wall between daughter nuclei after mitosis. The orientation of cell division depends on guidance of the phragmoplast during cytokinesis to a cortical site marked throughout prophase by another cytoskeletal structure called a preprophase band. Asymmetrically dividing cells become polarized and form asymmetric preprophase bands prior to mitosis; phragmoplasts are subsequently guided to these asymmetric cortical sites to form daughter cells of different shapes and/or sizes. Here we describe two new recessive mutations, discordia1 (dcd1) and discordia2 (dcd2), which disrupt the spatial regulation of cytokinesis during asymmetric cell divisions. Both mutations disrupt four classes of asymmetric cell divisions during the development of the maize leaf epidermis, without affecting the symmetric divisions through which most epidermal cells arise. The effects of dcd mutations on asymmetric cell division can be mimicked by cytochalasin D treatment, and divisions affected by dcd1 are hypersensitive to the effects of cytochalasin D. Analysis of actin and microtubule organization in these mutants showed no effect of either mutation on cell polarity, or on formation and localization of preprophase bands and spindles. In mutant cells, phragmoplasts in asymmetrically dividing cells are structurally normal and are initiated in the correct location, but often fail to move to the position formerly occupied by the preprophase band. We propose that dcd mutations disrupt an actin-dependent process necessary for the guidance of phragmoplasts during cytokinesis in asymmetrically dividing cells.

Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Human Blood ◽  
Asymmetric Cell Division ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

scholarly journals Emerging mechanisms of asymmetric stem cell division

2018 ◽  
Vol 217 (11) ◽  
pp. 3785-3795 ◽  
Author(s):  
Zsolt G. Venkei ◽  
Yukiko M. Yamashita
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Binary Outcomes ◽  
Cellular Mechanisms ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Dividing Cells ◽  
Stem Cell Division

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

scholarly journals Loss of DIAPH3, a Formin Family Protein, Leads to Cytokinetic Failure Only under High Temperature Conditions in Mouse FM3A Cells

2020 ◽  
Vol 21 (22) ◽  
pp. 8493
Author(s):  
Hiroki Kazama ◽  
Shu-ichiro Kashiwaba ◽  
Sayaka Ishii ◽  
Keiko Yoshida ◽  
Yuta Yatsuo ◽  
...  
Keyword(s):  
Cell Division ◽  
High Temperature ◽  
Temperature Sensitive ◽  
Dependent Manner ◽  
Temperature Dependent ◽  
Over Expression ◽  
Temperature Conditions ◽  
Family Protein ◽  
Temperature Environment ◽  
Ts Mutant

Cell division is essential for the maintenance of life and involves chromosome segregation and subsequent cytokinesis. The processes are tightly regulated at both the spatial and temporal level by various genes, and failures in this regulation are associated with oncogenesis. Here, we investigated the gene responsible for defects in cell division by using murine temperature-sensitive (ts) mutant strains, tsFT101 and tsFT50 cells. The ts mutants normally grow in a low temperature environment (32 °C) but fail to divide in a high temperature environment (39 °C). Exome sequencing and over-expression analyses identified Diaph3, a member of the formin family, as the cause of the temperature sensitivity observed in tsFT101 and tsFT50 cells. Interestingly, Diaph3 knockout cells showed abnormality in cytokinesis at 39 °C, and the phenotype was rescued by re-expression of Diaph3 WT, but not Diaph1 and Diaph2, other members of the formin family. Furthermore, Diaph3 knockout cells cultured at 39 °C showed a significant increase in the level of acetylated α-tubulin, an index of stabilized microtubules, and the level was reduced by Diaph3 expression. These results suggest that Diaph3 is required for cytokinesis only under high temperature conditions. Therefore, our study provides a new insight into the mechanisms by which regulatory factors of cell division function in a temperature-dependent manner.

scholarly journals Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins

2020 ◽  
Vol 28 (1) ◽  
pp. 108-122
Author(s):  
James M. Pemberton ◽  
Justin P. Pogmore ◽  
David W. Andrews
Keyword(s):  
Cell Death ◽  
Neuronal Apoptosis ◽  
Axonal Degeneration ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Axon Degeneration ◽  
Mitochondrial Outer Membrane ◽  
Future Research ◽  
System Disease ◽  
Family Protein

AbstractAxonal degeneration and neuronal cell death are fundamental processes in development and contribute to the pathology of neurological disease in adults. Both processes are regulated by BCL-2 family proteins which orchestrate the permeabilization of the mitochondrial outer membrane (MOM). MOM permeabilization (MOMP) results in the activation of pro-apoptotic molecules that commit neurons to either die or degenerate. With the success of small-molecule inhibitors targeting anti-apoptotic BCL-2 proteins for the treatment of lymphoma, we can now envision the use of inhibitors of apoptosis with exquisite selectivity for BCL-2 family protein regulation of neuronal apoptosis in the treatment of nervous system disease. Critical to this development is deciphering which subset of proteins is required for neuronal apoptosis and axon degeneration, and how these two different outcomes are separately regulated. Moreover, noncanonical BCL-2 family protein functions unrelated to the regulation of MOMP, including impacting necroptosis and other modes of cell death may reveal additional potential targets and/or confounders. This review highlights our current understanding of BCL-2 family mediated neuronal cell death and axon degeneration, while identifying future research questions to be resolved to enable regulating neuronal survival pharmacologically.

scholarly journals PHYL Acts to Down-Regulate TTK88, a Transcriptional Repressor of Neuronal Cell Fates, by a SINA-Dependent Mechanism

Cell ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 459-467 ◽  
Author(s):  
Amy H Tang ◽  
Thomas P Neufeld ◽  
Elaine Kwan ◽  
Gerald M Rubin
Keyword(s):  
Transcriptional Repressor ◽  
Neuronal Cell ◽  
Cell Fates ◽  
Dependent Mechanism

scholarly journals Structure of the MarR family protein Rv0880 fromMycobacterium tuberculosis

2015 ◽  
Vol 71 (6) ◽  
pp. 741-745 ◽  
Author(s):  
Yun-Rong Gao ◽  
Na Feng ◽  
Tao Chen ◽  
De-Feng Li ◽  
Li-Jun Bi
Keyword(s):  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
Isoelectric Point ◽  
Unit Cell Parameters ◽  
Dimerization Domain ◽  
Winged Helix ◽  
Cell Parameters ◽  
Transcription Regulator ◽  
Pfam Database ◽  
Family Protein

Rv0880 from the pathogenMycobacterium tuberculosisis classified as a MarR family protein in the Pfam database. It consists of 143 amino acids and has an isoelectric point of 10.9. Crystals of Rv0880 belonged to space groupP1, with unit-cell parametersa= 54.97,b= 69.60,c= 70.32 Å, α = 103.71, β = 111.06, γ = 105.83°. The structure of the MarR family transcription regulator Rv0880 was solved at a resolution of 2.0 Å with anRcrystandRfreeof 21.2 and 24.9%, respectively. The dimeric structure resembles that of other MarR proteins, with each subunit comprising a winged helix–turn–helix domain connected to an α-helical dimerization domain.

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