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

Vincent Bertrand

doi:10.1002/wdev.228

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

The Journal of Cell Biology ◽

10.1083/jcb.200803071 ◽

2008 ◽

Vol 182 (6) ◽

pp. 1063-1071 ◽

Cited By ~ 58

Author(s):

Sachin Hebbar ◽

Mariano T. Mesngon ◽

Aimee M. Guillotte ◽

Bhavim Desai ◽

Ramses Ayala ◽

...

Keyword(s):

Nuclear Envelope ◽

Cell Fate ◽

Ventricular Zone ◽

Mitotic Cell ◽

Cytoplasmic Dynein ◽

Developmental Defects ◽

Animal Development ◽

Cell Fate Decisions ◽

Nuclear Envelope Breakdown ◽

Neural Cell Fate

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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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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