scholarly journals LKB1 specifies neural crest cell fates through pyruvate-alanine cycling

2019 ◽  
Vol 5 (7) ◽  
pp. eaau5106 ◽  
Author(s):  
Anca G. Radu ◽  
Sakina Torch ◽  
Florence Fauvelle ◽  
Karin Pernet-Gallay ◽  
Anthony Lucas ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Crest Cell ◽  
Dependent Manner ◽  
Cell Fates ◽  
Neural Crest Stem Cells ◽  
Metabolomic Profiling ◽  
Intestinal Pseudo Obstruction ◽  
Migratory Cells ◽  
Hind Limb Paralysis

Metabolic processes underlying the development of the neural crest, an embryonic population of multipotent migratory cells, are poorly understood. Here, we report that conditional ablation of the Lkb1 tumor suppressor kinase in mouse neural crest stem cells led to intestinal pseudo-obstruction and hind limb paralysis. This phenotype originated from a postnatal degeneration of the enteric nervous ganglia and from a defective differentiation of Schwann cells. Metabolomic profiling revealed that pyruvate-alanine conversion is enhanced in the absence of Lkb1. Mechanistically, inhibition of alanine transaminases restored glial differentiation in an mTOR-dependent manner, while increased alanine level directly inhibited the glial commitment of neural crest cells. Treatment with the metabolic modulator AICAR suppressed mTOR signaling and prevented Schwann cell and enteric defects of Lkb1 mutant mice. These data uncover a link between pyruvate-alanine cycling and the specification of glial cell fate with potential implications in the understanding of the molecular pathogenesis of neural crest diseases.

scholarly journals The neural crest stem cells: control of neural crest cell fate and plasticity by endothelin-3

2001 ◽  
Vol 73 (4) ◽  
pp. 533-545 ◽  
Author(s):  
ELISABETH DUPIN ◽  
CARLA REAL ◽  
NICOLE LeDOUARIN
Keyword(s):  
Stem Cells ◽  
Neural Crest ◽  
Cell Fate ◽  
Neural Crest Cell ◽  
Cell Types ◽  
The Body ◽  
Neural Crest Stem Cells ◽  
Environmental Signals

How the considerable diversity of neural crest (NC)-derived cell types arises in the vertebrate embryo has long been a key question in developmental biology. The pluripotency and plasticity of differentiation of the NC cell population has been fully documented and it is well-established that environmental cues play an important role in patterning the NC derivatives throughout the body. Over the past decade, in vivo and in vitro cellular approaches have unravelled the differentiation potentialities of single NC cells and led to the discovery of NC stem cells. Although it is clear that the final fate of individual cells is in agreement with their final position within the embryo, it has to be stressed that the NC cells that reach target sites are pluripotent and further restrictions occur only late in development. It is therefore a heterogenous collection of cells that is submitted to local environmental signals in the various NC-derived structures. Several factors were thus identified which favor the development of subsets of NC-derived cells in vitro. Moreover, the strategy of gene targeting in mouse has led at identifying new molecules able to control one or several aspects of NC cell differentiation in vivo. Endothelin peptides (and endothelin receptors) are among those. The conjunction of recent data obtained in mouse and avian embryos and reviewed here contributes to a better understanding of the action of the endothelin signaling pathway in the emergence and stability of NC-derived cell phenotypes.

Timing and pattern of cell fate restrictions in the neural crest lineage

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4351-4359 ◽  
Author(s):  
P.D. Henion ◽  
J.A. Weston
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Precursor Cells ◽  
Cell Fates ◽  
Distinct Cell ◽  
Ventral Pathway ◽  
Neural Crest Cell Migration

The trunk neural crest of vertebrate embryos is a transient collection of precursor cells present along the dorsal aspect of the neural tube. These cells migrate on two distinct pathways and give rise to specific derivatives in precise embryonic locations. One group of crest cells migrates early on a ventral pathway and generates neurons and glial cells. A later-dispersing group migrates laterally and gives rise to melanocytes in the skin. These observations raise the possibility that the appearance of distinct derivatives in different embryonic locations is a consequence of lineage restrictions specified before or soon after the onset of neural crest cell migration. To test this notion, we have assessed when and in what order distinct cell fates are specified during neural crest development. We determined the proportions of different types of precursor cells in cultured neural crest populations immediately after emergence from the neural tube and at intervals as development proceeds. We found that the initial neural crest population was a heterogeneous mixture of precursors almost half of which generated single-phenotype clones. Distinct neurogenic and melanogenic sublineages were also present in the outgrowth population almost immediately, but melanogenic precursors dispersed from the neural tube only after many neurogenic precursors had already done so. A discrete fate-restricted neuronal precursor population was distinguished before entirely separate fate-restricted melanocyte and glial precursor populations were present, and well before initial neuronal differentiation. Taken together, our results demonstrate that lineage-restricted subpopulations constitute a major portion of the initial neural crest population and that neural crest diversification occurs well before overt differentiation by the asynchronous restriction of distinct cell fates. Thus, the different morphogenetic and differentiative behavior of neural crest subsets in vivo may result from earlier cell fate-specification events that generate developmentally distinct subpopulations that respond differentially to environmental cues.

scholarly journals Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

2013 ◽  
Vol 203 (4) ◽  
pp. 673-689 ◽  
Author(s):  
Ah-Lai Law ◽  
Anne Vehlow ◽  
Maria Kotini ◽  
Lauren Dodgson ◽  
Daniel Soong ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Direct Interaction ◽  
Dependent Manner ◽  
Border Cell ◽  
Promote Cell Migration ◽  
Wave Complex

Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo.

scholarly journals The Hippo pathway member YAP enhances human neural crest cell fate and migration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Christopher J. Hindley ◽  
Alexandra Larisa Condurat ◽  
Vishal Menon ◽  
Ria Thomas ◽  
Luis M. Azmitia ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Hippo Pathway ◽  
Neural Crest Cell ◽  
And Migration ◽  
The Hippo Pathway ◽  
Crest Cell

scholarly journals Metalloprotease-Dependent Attenuation of BMP Signaling Restricts Cardiac Neural Crest Cell Fate

Cell Reports ◽  
2019 ◽  
Vol 29 (3) ◽  
pp. 603-616.e5
Author(s):  
Hiroyuki N. Arai ◽  
Fuminori Sato ◽  
Takuya Yamamoto ◽  
Knut Woltjen ◽  
Hiroshi Kiyonari ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Crest Cell ◽  
Bmp Signaling ◽  
Cardiac Neural Crest ◽  
Crest Cell

Regulation of cranial neural crest cell fate by Irf6 and Twist1 interaction

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Walid D. Fakhouri ◽  
Jessica Wildgrube Bertol ◽  
Victoria K. Xie ◽  
Shelby Johnston ◽  
Kelsea Hubka ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Neural Crest Cell ◽  
Cranial Neural Crest ◽  
Cranial Neural Crest Cell ◽  
Crest Cell

scholarly journals Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Debadrita Bhattacharya ◽  
Megan Rothstein ◽  
Ana Paula Azambuja ◽  
Marcos Simoes-Costa
Keyword(s):  
Cell Differentiation ◽  
Neural Crest ◽  
Positional Information ◽  
Cell Types ◽  
Transcriptional Networks ◽  
Dependent Manner ◽  
Regulatory Circuit ◽  
Distinct Cell ◽  
Cell Niche ◽  
Migratory Cells

A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.

scholarly journals Opposing effects of Wnt/β-catenin signaling on epithelial and mesenchymal cell fate in the developing cochlea

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Sara E. Billings ◽  
Nina M. Myers ◽  
Lee Quiruz ◽  
Alan G. Cheng
Keyword(s):  
Cell Fate ◽  
Mesenchymal Cell ◽  
Lateral Wall ◽  
Mesenchymal Cells ◽  
Sensory Cells ◽  
Dependent Manner ◽  
Cell Fates ◽  
Proliferation And Differentiation ◽  
A Cell ◽  
Opposing Effects

ABSTRACT During embryonic development, the otic epithelium and surrounding periotic mesenchymal cells originate from distinct lineages and coordinate to form the mammalian cochlea. Epithelial sensory precursors within the cochlear duct first undergo terminal mitosis before differentiating into sensory and non-sensory cells. In parallel, periotic mesenchymal cells differentiate to shape the lateral wall, modiolus and pericochlear spaces. Previously, Wnt activation was shown to promote proliferation and differentiation of both otic epithelial and mesenchymal cells. Here, we fate-mapped Wnt-responsive epithelial and mesenchymal cells in mice and found that Wnt activation resulted in opposing cell fates. In the post-mitotic cochlear epithelium, Wnt activation via β-catenin stabilization induced clusters of proliferative cells that dedifferentiated and lost epithelial characteristics. In contrast, Wnt-activated periotic mesenchyme formed ectopic pericochlear spaces and cell clusters showing a loss of mesenchymal and gain of epithelial features. Finally, clonal analyses via multi-colored fate-mapping showed that Wnt-activated epithelial cells proliferated and formed clonal colonies, whereas Wnt-activated mesenchymal cells assembled as aggregates of mitotically quiescent cells. Together, we show that Wnt activation drives transition between epithelial and mesenchymal states in a cell type-dependent manner.

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