A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border

In Xenopus, the neural plate border gives rise to at least three cell populations: the neural crest, the preplacodal ectoderm, and the hatching gland. To understand the molecular mechanisms that regulate the formation of these lineages, we have analyzed the role of two transcription factors, Pax3 and Zic1, which are among the earliest genes activated in response to neural plate border-inducing signals. At the end of gastrulation, Pax3 and Zic1 are coexpressed in the neural crest forming region. In addition, Pax3 is expressed in progenitors of the hatching gland, and Zic1 is detected in the preplacodal ectoderm. Using gain of function and knockdown approaches in whole embryos and animal explants, we demonstrate that Pax3 and Zic1 are necessary and sufficient to promote hatching gland and preplacodal fates, respectively, whereas their combined activity is essential to specify the neural crest. Moreover, we show that by manipulating the levels of Pax3 and Zic1 it is possible to shift fates among these cells. These findings provide novel information on the mechanisms regulating cell fate decisions at the neural plate border.

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Decision letter: Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

10.7554/elife.21620.031 ◽

2016 ◽

Keyword(s):

Cell Fate ◽

Neural Plate ◽

Border Cells ◽

Transcriptional Signature ◽

Neural Plate Border

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Data‐driven modelling of a gene regulatory network for cell fate decisions in the growing limb bud

Molecular Systems Biology ◽

10.15252/msb.20145882 ◽

2015 ◽

Vol 11 (7) ◽

pp. 815 ◽

Cited By ~ 25

Author(s):

Manu Uzkudun ◽

Luciano Marcon ◽

James Sharpe

Keyword(s):

Gene Regulatory Network ◽

Cell Fate ◽

Regulatory Network ◽

Limb Bud ◽

Data Driven ◽

Cell Fate Decisions ◽

Gene Regulatory

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prdm1a and olig4 act downstream of Notch signaling to regulate cell fate at the neural plate border

Developmental Biology ◽

10.1016/j.ydbio.2011.06.005 ◽

2011 ◽

Vol 356 (2) ◽

pp. 496-505 ◽

Cited By ~ 19

Author(s):

Laura Hernandez-Lagunas ◽

Davalyn R. Powell ◽

Jera Law ◽

Kelly A. Grant ◽

Kristin Bruk Artinger

Keyword(s):

Notch Signaling ◽

Cell Fate ◽

Neural Plate ◽

Neural Plate Border

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Logical modeling of lymphoid and myeloid cell specification and transdifferentiation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1610622114 ◽

2017 ◽

Vol 114 (23) ◽

pp. 5792-5799 ◽

Cited By ~ 51

Author(s):

Samuel Collombet ◽

Chris van Oevelen ◽

Jose Luis Sardina Ortega ◽

Wassim Abou-Jaoudé ◽

Bruno Di Stefano ◽

...

Keyword(s):

Transcription Factors ◽

Cell Fate ◽

Regulatory Network ◽

Developmental Process ◽

Ectopic Expression ◽

Myeloid Cell ◽

Hematopoietic Stem ◽

Chip Sequencing ◽

Cell Fate Decisions ◽

Public Data

Blood cells are derived from a common set of hematopoietic stem cells, which differentiate into more specific progenitors of the myeloid and lymphoid lineages, ultimately leading to differentiated cells. This developmental process is controlled by a complex regulatory network involving cytokines and their receptors, transcription factors, and chromatin remodelers. Using public data and data from our own molecular genetic experiments (quantitative PCR, Western blot, EMSA) or genome-wide assays (RNA-sequencing, ChIP-sequencing), we have assembled a comprehensive regulatory network encompassing the main transcription factors and signaling components involved in myeloid and lymphoid development. Focusing on B-cell and macrophage development, we defined a qualitative dynamical model recapitulating cytokine-induced differentiation of common progenitors, the effect of various reported gene knockdowns, and the reprogramming of pre-B cells into macrophages induced by the ectopic expression of specific transcription factors. The resulting network model can be used as a template for the integration of new hematopoietic differentiation and transdifferentiation data to foster our understanding of lymphoid/myeloid cell-fate decisions.

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Cell-to-cell ATP differences can modulate cellular decision-making

Access Microbiology ◽

10.1099/acmi.ac2020.po0179 ◽

2020 ◽

Vol 2 (7A) ◽

Author(s):

Ryan Kerr ◽

Sara Jabbari ◽

Iain Johnston

Keyword(s):

Decision Making ◽

Cell Fate ◽

Regulatory Network ◽

Phenotypic Diversity ◽

Biological Systems ◽

Energy Budgets ◽

Specific Cell ◽

Cell Fate Decisions ◽

Cellular Decision Making ◽

Intracellular Energy

Cells generate phenotypic diversity both during development and in response to stressful and changing environments, aiding survival. Functionally vital cell fate decisions from a range of phenotypic choices are made by regulatory networks, the dynamics of which rely on gene expression and hence depend on the cellular energy budget (and particularly ATP levels). However, despite pronounced cell-to-cell ATP differences observed across biological systems, the influence of energy availability on regulatory network dynamics is often overlooked as a cellular decision-making modulator, limiting our knowledge of how energy budgets affect cell behaviour. Here, we consider a mathematical model of a highly generalisable, ATP-dependent, decision-making regulatory network, and show that cell-to-cell ATP variability changes the sets of decisions a cell can make. Our model shows that increasing intracellular energy levels can increase the number of supported stable phenotypes, corresponding to increased decision-making capacity. Model cells with sub-threshold intracellular energy are limited to a singular phenotype, forcing the adoption of a specific cell fate. We suggest that energetic differences between cells may be an important consideration to help explain observed variability in cellular decision-making across a broad range of biological systems, including bacteria and the blood stem cell system.

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Intracellular Energy Variability Modulates Cellular Decision-Making Capacity

Scientific Reports ◽

10.1038/s41598-019-56587-5 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Ryan Kerr ◽

Sara Jabbari ◽

Iain G. Johnston

Keyword(s):

Decision Making ◽

Cell Fate ◽

Regulatory Network ◽

Phenotypic Diversity ◽

Biological Systems ◽

Specific Cell ◽

Cell Fate Decisions ◽

Cellular Decision Making ◽

Decision Making Capacity ◽

Intracellular Energy

AbstractCells generate phenotypic diversity both during development and in response to stressful and changing environments, aiding survival. Functionally vital cell fate decisions from a range of phenotypic choices are made by regulatory networks, the dynamics of which rely on gene expression and hence depend on the cellular energy budget (and particularly ATP levels). However, despite pronounced cell-to-cell ATP differences observed across biological systems, the influence of energy availability on regulatory network dynamics is often overlooked as a cellular decision-making modulator, limiting our knowledge of how energy budgets affect cell behaviour. Here, we consider a mathematical model of a highly generalisable, ATP-dependent, decision-making regulatory network, and show that cell-to-cell ATP variability changes the sets of decisions a cell can make. Our model shows that increasing intracellular energy levels can increase the number of supported stable phenotypes, corresponding to increased decision-making capacity. Model cells with sub-threshold intracellular energy are limited to a singular phenotype, forcing the adoption of a specific cell fate. We suggest that energetic differences between cells may be an important consideration to help explain observed variability in cellular decision-making across biological systems.

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prdm1a regulates Rohon-Beard neuron and neural crest cell fate at the neural plate border

Developmental Biology ◽

10.1016/j.ydbio.2010.05.309 ◽

2010 ◽

Vol 344 (1) ◽

pp. 500

Author(s):

Jera Law ◽

Kristin B. Artinger

Keyword(s):

Neural Crest ◽

Cell Fate ◽

Neural Crest Cell ◽

Neural Plate ◽

Neural Plate Border ◽

Crest Cell

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Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

eLife ◽

10.7554/elife.21620 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 27

Author(s):

Daniela Roellig ◽

Johanna Tan-Cabugao ◽

Sevan Esaian ◽

Marianne E Bronner

Keyword(s):

Neural Crest ◽

Cell Fate ◽

Neural Tube ◽

Temporal Analysis ◽

Neural Plate ◽

Neural Tube Closure ◽

Border Cells ◽

Transcriptional Signature ◽

Neural Plate Border ◽

Tube Versus

The ‘neural plate border’ of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

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