Lis1 and Ndel1 influence the timing of nuclear envelope breakdown in neural stem cells

Lis1 and Ndel1 are essential for animal development. They interact directly with one another and with cytoplasmic dynein. The developing brain is especially sensitive to reduced Lis1 or Ndel1 levels, as both proteins influence spindle orientation, neural cell fate decisions, and neuronal migration. We report here that Lis1 and Ndel1 reduction in a mitotic cell line impairs prophase nuclear envelope (NE) invagination (PNEI). This dynein-dependent process facilitates NE breakdown (NEBD) and occurs before the establishment of the bipolar spindle. Ndel1 phosphorylation is important for this function, regulating binding to both Lis1 and dynein. Prophase cells in the ventricular zone (VZ) of embryonic day 13.5 Lis1+/− mouse brains show reduced PNEI, and the ratio of prophase to prometaphase cells is increased, suggesting an NEBD delay. Moreover, prophase cells in the VZ contain elevated levels of Ndel1 phosphorylated at a key cdk5 site. Our data suggest that a delay in NEBD in the VZ could contribute to developmental defects associated with Lis1–Ndel1 disruption.

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Tbx6 is a determinant of cardiac and neural cell fate decisions in multipotent P19CL6 cells

Differentiation ◽

10.1016/j.diff.2012.04.007 ◽

2012 ◽

Vol 84 (2) ◽

pp. 176-184 ◽

Cited By ~ 5

Author(s):

Svetlana Gavrilov ◽

Thomas G. Nührenberg ◽

Anthony W. Ashton ◽

Chang-Fu Peng ◽

Jennifer C. Moore ◽

...

Keyword(s):

Cell Fate ◽

Neural Cell ◽

Cell Fate Decisions ◽

P19cl6 Cells ◽

Neural Cell Fate

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Faculty Opinions recommendation of Cytoplasmic dynein as a facilitator of nuclear envelope breakdown.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1004048.45704 ◽

2002 ◽

Author(s):

Viki Allan

Keyword(s):

Nuclear Envelope ◽

Cytoplasmic Dynein ◽

Nuclear Envelope Breakdown

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aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in Drosophila neuroblasts

eLife ◽

10.7554/elife.29939 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 14

Author(s):

Matthew Robert Hannaford ◽

Anne Ramat ◽

Nicolas Loyer ◽

Jens Januschke

Keyword(s):

Cell Cycle ◽

Nervous System ◽

Plasma Membrane ◽

Nuclear Envelope ◽

Cell Fate ◽

Progenitor Cell ◽

Adapter Protein ◽

Unequal Distribution ◽

Nuclear Envelope Breakdown ◽

Differential Binding

Cell fate assignment in the nervous system of vertebrates and invertebrates often hinges on the unequal distribution of molecules during progenitor cell division. We address asymmetric fate determinant localization in the developing Drosophila nervous system, specifically the control of the polarized distribution of the cell fate adapter protein Miranda. We reveal a step-wise polarization of Miranda in larval neuroblasts and find that Miranda’s dynamics and cortical association are differently regulated between interphase and mitosis. In interphase, Miranda binds to the plasma membrane. Then, before nuclear envelope breakdown, Miranda is phosphorylated by aPKC and displaced into the cytoplasm. This clearance is necessary for the subsequent establishment of asymmetric Miranda localization. After nuclear envelope breakdown, actomyosin activity is required to maintain Miranda asymmetry. Therefore, phosphorylation by aPKC and differential binding to the actomyosin network are required at distinct phases of the cell cycle to polarize fate determinant localization in neuroblasts.

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β‐catenin‐driven binary cell fate decisions in animal development

Wiley Interdisciplinary Reviews Developmental Biology ◽

10.1002/wdev.228 ◽

2016 ◽

Vol 5 (3) ◽

pp. 377-388 ◽

Cited By ~ 9

Author(s):

Vincent Bertrand

Keyword(s):

Cell Fate ◽

Animal Development ◽

Cell Fate Decisions

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Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease

Scientifica ◽

10.6064/2012/480129 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Volney L. Sheen

Keyword(s):

Cell Fate ◽

Brain Size ◽

Ventricular Zone ◽

Cortical Development ◽

Cell Fate Decisions ◽

Cytoskeletal Network ◽

Malformation Of Cortical Development ◽

Periventricular Heterotopia ◽

Mature Neurons ◽

Radial Glial

During cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions and consequent expansion of the progenitor pool, as well as impact the integrity of the neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial scaffolding and alters initial neuronal migration from the ventricular zone. Vesicle trafficking is also required for maintenance of lipid and protein cycling within the leading and trailing edge of migratory neurons, as well as dendrites and synapses of mature neurons. Defects in this transport machinery disrupt neuronal identity, migration, and connectivity and give rise to a malformation of cortical development termed as periventricular heterotopia (PH). PH is characterized by a reduction in brain size, ectopic clusters of neurons localized along the lateral ventricle, and epilepsy and dyslexia. These anatomical anomalies correlate with developmental impairments in neural progenitor proliferation and specification, migration from loss of neuroependymal integrity and neuronal motility, and aberrant neuronal process extension. Genes causal for PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network. This paper explores the role of these dynamic processes in cortical development and disease.

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aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in Drosophila neuroblasts

10.1101/148213 ◽

2017 ◽

Author(s):

Matthew Hannaford ◽

Anne Ramat ◽

Nicolas Loyer ◽

Jens Januschke

Keyword(s):

Cell Cycle ◽

Nervous System ◽

Plasma Membrane ◽

Cell Division ◽

Nuclear Envelope ◽

Cell Fate ◽

Progenitor Cell ◽

Unequal Distribution ◽

Nuclear Envelope Breakdown ◽

Differential Binding

SUMMARYCell fate generation can rely on the unequal distribution of molecules during progenitor cell division in the nervous system of vertebrates and invertebrates. Here we address asymmetric fate determinant localization in the developing Drosophila nervous system, focussing on the control of asymmetric Miranda distribution in larval neuroblasts. We used live imaging of neuroblast polarity reporters at endogenous levels of expression to address Miranda localization during the cell cycle. We reveal that the regulation and dynamics of cortical association of Miranda in interphase and mitosis are different. In interphase Miranda binds directly to the plasma membrane. At the onset of mitosis, Miranda is phosphorylated by aPKC and displaced from the PM. After nuclear envelope breakdown asymmetric localization of Miranda requires actomyosin activity. Therefore, Miranda phosphorylation by aPKC and differential binding to the actomyosin network are required at distinct phases of the cell cycle to polarize fate determinant localization.

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Functional Coordination of Three Mitotic Motors inDrosophila Embryos

Molecular Biology of the Cell ◽

10.1091/mbc.11.1.241 ◽

2000 ◽

Vol 11 (1) ◽

pp. 241-253 ◽

Cited By ~ 166

Author(s):

David J. Sharp ◽

Heather M. Brown ◽

Mijung Kwon ◽

Gregory C. Rogers ◽

Gina Holland ◽

...

Keyword(s):

Nuclear Envelope ◽

Cytoplasmic Dynein ◽

Spindle Pole ◽

Nuclear Envelope Breakdown ◽

Mitotic Motors ◽

Balance Of Forces ◽

Spindle Elongation ◽

And Function ◽

Anaphase B ◽

Drosophila Embryos

It is well established that multiple microtubule-based motors contribute to the formation and function of the mitotic spindle, but how the activities of these motors interrelate remains unclear. Here we visualize spindle formation in living Drosophila embryos to show that spindle pole movements are directed by a temporally coordinated balance of forces generated by three mitotic motors, cytoplasmic dynein, KLP61F, and Ncd. Specifically, our findings suggest that dynein acts to move the poles apart throughout mitosis and that this activity is augmented by KLP61F after the fenestration of the nuclear envelope, a process analogous to nuclear envelope breakdown, which occurs at the onset of prometaphase. Conversely, we find that Ncd generates forces that pull the poles together between interphase and metaphase, antagonizing the activity of both dynein and KLP61F and serving as a brake for spindle assembly. During anaphase, however, Ncd appears to have no effect on spindle pole movements, suggesting that its activity is down-regulated at this time, allowing dynein and KLP61F to drive spindle elongation during anaphase B.

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Positive autoregulation of lag-1 in response to LIN-12 activation in cell fate decisions during C. elegans reproductive system development

Development ◽

10.1242/dev.193482 ◽

2020 ◽

Vol 147 (18) ◽

pp. dev193482

Author(s):

Katherine Leisan Luo ◽

Ryan S. Underwood ◽

Iva Greenwald

Keyword(s):

Cell Fate ◽

Reproductive System ◽

Target Gene ◽

System Development ◽

Animal Development ◽

Cell Fate Decisions ◽

C Elegans ◽

Spatiotemporal Regulation ◽

Target Gene Transcription ◽

Notch Activation

ABSTRACTDuring animal development, ligand binding releases the intracellular domain of LIN-12/Notch by proteolytic cleavage to translocate to the nucleus, where it associates with the DNA-binding protein LAG-1/CSL to activate target gene transcription. We investigated the spatiotemporal regulation of LAG-1/CSL expression in Caenorhabditis elegans and observed that an increase in endogenous LAG-1 levels correlates with LIN-12/Notch activation in different cell contexts during reproductive system development. We show that this increase is via transcriptional upregulation by creating a synthetic endogenous operon, and identified an enhancer region that contains multiple LAG-1 binding sites (LBSs) embedded in a more extensively conserved high occupancy target (HOT) region. We show that these LBSs are necessary for upregulation in response to LIN-12/Notch activity, indicating that lag-1 engages in direct positive autoregulation. Deletion of the HOT region from endogenous lag-1 reduced LAG-1 levels and abrogated positive autoregulation, but did not cause hallmark cell fate transformations associated with loss of lin-12/Notch or lag-1 activity. Instead, later somatic reproductive system defects suggest that proper transcriptional regulation of lag-1 confers robustness to somatic reproductive system development.

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