Exogenous retinoic acid decreases in vivo and in vitro proliferative activity during the early migratory stage of neural crest cells

β-Catenin plays a pivotal role in cadherin-mediated cell adhesion. Moreover, it is a downstream signaling component of Wnt that controls multiple developmental processes such as cell proliferation, apoptosis, and fate decisions. To study the role of β-catenin in neural crest development, we used the Cre/loxP system to ablate β-catenin specifically in neural crest stem cells. Although several neural crest–derived structures develop normally, mutant animals lack melanocytes and dorsal root ganglia (DRG). In vivo and in vitro analyses revealed that mutant neural crest cells emigrate but fail to generate an early wave of sensory neurogenesis that is normally marked by the transcription factor neurogenin (ngn) 2. This indicates a role of β-catenin in premigratory or early migratory neural crest and points to heterogeneity of neural crest cells at the earliest stages of crest development. In addition, migratory neural crest cells lateral to the neural tube do not aggregate to form DRG and are unable to produce a later wave of sensory neurogenesis usually marked by the transcription factor ngn1. We propose that the requirement of β-catenin for the specification of melanocytes and sensory neuronal lineages reflects roles of β-catenin both in Wnt signaling and in mediating cell–cell interactions.

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Trophic and proliferative perturbations of in vivo/in vitro cephalic neural crest cells after ethanol exposure are prevented by Neurotrophin 3

Neurotoxicology and Teratology ◽

10.1016/j.ntt.2011.03.003 ◽

2011 ◽

Vol 33 (3) ◽

pp. 422-430 ◽

Cited By ~ 17

Author(s):

María B. Jaurena ◽

Néstor G. Carri ◽

Natalia L. Battiato ◽

Roberto A. Rovasio

Keyword(s):

Neural Crest ◽

Neural Crest Cells ◽

Ethanol Exposure ◽

Neurotrophin 3

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Cadherin-6B is proteolytically processed during epithelial-to-mesenchymal transitions of the cranial neural crest

Molecular Biology of the Cell ◽

10.1091/mbc.e13-08-0459 ◽

2014 ◽

Vol 25 (1) ◽

pp. 41-54 ◽

Cited By ~ 44

Author(s):

Andrew T. Schiffmacher ◽

Rangarajan Padmanabhan ◽

Sharon Jhingory ◽

Lisa A. Taneyhill

Keyword(s):

Neural Crest ◽

Epithelial To Mesenchymal Transition ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Spatiotemporal Pattern ◽

Cranial Neural Crest ◽

Mesenchymal Transition ◽

Crest Cell

The epithelial-to-mesenchymal transition (EMT) is a highly coordinated process underlying both development and disease. Premigratory neural crest cells undergo EMT, migrate away from the neural tube, and differentiate into diverse cell types during vertebrate embryogenesis. Adherens junction disassembly within premigratory neural crest cells is one component of EMT and, in chick cranial neural crest cells, involves cadherin-6B (Cad6B) down-regulation. Whereas Cad6B transcription is repressed by Snail2, the rapid loss of Cad6B protein during EMT is suggestive of posttranslational mechanisms that promote Cad6B turnover. For the first time in vivo, we demonstrate Cad6B proteolysis during neural crest cell EMT, which generates a Cad6B N-terminal fragment (NTF) and two C-terminal fragments (CTF1/2). Coexpression of relevant proteases with Cad6B in vitro shows that a disintegrin and metalloproteinases (ADAMs) ADAM10 and ADAM19, together with γ-secretase, cleave Cad6B to produce the NTF and CTFs previously observed in vivo. Of importance, both ADAMs and γ-secretase are expressed in the appropriate spatiotemporal pattern in vivo to proteolytically process Cad6B. Overexpression or depletion of either ADAM within premigratory neural crest cells prematurely reduces or maintains Cad6B, respectively. Collectively these results suggest a dual mechanism for Cad6B proteolysis involving two ADAMs, along with γ-secretase, during cranial neural crest cell EMT.

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MAPRE2 mutations result in altered human cranial neural crest migration, underlying craniofacial malformations in CSC-KT syndrome

Scientific Reports ◽

10.1038/s41598-021-83771-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cedric Thues ◽

Jorge S. Valadas ◽

Liesbeth Deaulmerie ◽

Ann Geens ◽

Amit K. Chouhan ◽

...

Keyword(s):

Neural Crest ◽

Induced Pluripotent Stem Cell ◽

Neural Crest Cells ◽

Branchial Arch ◽

Cellular Migration ◽

Cranial Neural Crest ◽

Craniofacial Malformations ◽

Neural Crest Migration

AbstractCircumferential skin creases (CSC-KT) is a rare polymalformative syndrome characterised by intellectual disability associated with skin creases on the limbs, and very characteristic craniofacial malformations. Previously, heterozygous and homozygous mutations in MAPRE2 were found to be causal for this disease. MAPRE2 encodes for a member of evolutionary conserved microtubule plus end tracking proteins, the end binding (EB) family. Unlike MAPRE1 and MAPRE3, MAPRE2 is not required for the persistent growth and stabilization of microtubules, but plays a role in other cellular processes such as mitotic progression and regulation of cell adhesion. The mutations identified in MAPRE2 all reside within the calponin homology domain, responsible to track and interact with the plus-end tip of growing microtubules, and previous data showed that altered dosage of MAPRE2 resulted in abnormal branchial arch patterning in zebrafish. In this study, we developed patient derived induced pluripotent stem cell lines for MAPRE2, together with isogenic controls, using CRISPR/Cas9 technology, and differentiated them towards neural crest cells with cranial identity. We show that changes in MAPRE2 lead to alterations in neural crest migration in vitro but also in vivo, following xenotransplantation of neural crest progenitors into developing chicken embryos. In addition, we provide evidence that changes in focal adhesion might underlie the altered cell motility of the MAPRE2 mutant cranial neural crest cells. Our data provide evidence that MAPRE2 is involved in cellular migration of cranial neural crest and offers critical insights into the mechanism underlying the craniofacial dysmorphisms and cleft palate present in CSC-KT patients. This adds the CSC-KT disorder to the growing list of neurocristopathies.

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Effects of vitamin A on the behaviour of migratory neural crest cells in vitro

Journal of Cell Science ◽

10.1242/jcs.57.1.331 ◽

1982 ◽

Vol 57 (1) ◽

pp. 331-350 ◽

Cited By ~ 2

Author(s):

P. Thorogood ◽

L. Smith ◽

A. Nicol ◽

R. McGinty ◽

D. Garrod

Keyword(s):

Cell Surface ◽

Neural Crest ◽

Neural Crest Cells ◽

Initial Exposure ◽

Normal Medium ◽

Locomotory Behaviour ◽

Cranial Neural Crest Cells ◽

In Vivo Effects

It has been proposed elsewhere that the teratogenic effects of retinoids on craniofacial morphogenesis are caused by a disturbance of the migration of cranial neural crest cells. The effects of 3.5 X 10(−5) M and 3.5 X 10(−6) M-retinol on the migration of avian neural crest cells in vitro have been investigated by monitoring cell morphology, locomotory behaviour, fibronectin distribution and actin-microfilament organization. Retinol retards migration by affecting cell-to-substratum adhesiveness. Cells exposed to medium containing retinol are less adherent to the substratum, and although the cell surface is very mobile, are unable to extend or maintain lamellipodia. As a consequence the cells do not actively translocate. Fibronectin distribution at the cell surface is sparse, possibly as a result of shedding, and actin distribution remains diffuse. At the retinol molarities used all these effects are reversible. Thus cells allowed to recover in normal medium flatten out, display lamellipodia and commence active translocation. Fibronectin becomes organized into a fibrillar array and actin microfilaments become organized into cables. The period needed for this recovery is directly related to the molarity of retinol during the initial exposure; after recovery the retinol-treated cells are virtually indistinguishable from control cells. We propose that in vivo the effects of retinoids might be to impair cell-extracellular matrix interaction, thus impeding a cell's ability to migrate through that matrix. Contrary to previous suggestions, the in vivo effects are probably not in any way ‘specific’ to neural crest cells but are more accurately considered as ‘selective’, in that any cell undergoing migration would be similarly affected.

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How inhibitory cues can both constrain and promote cell migration

The Journal of Cell Biology ◽

10.1083/jcb.201605074 ◽

2016 ◽

Vol 213 (5) ◽

pp. 505-507 ◽

Cited By ~ 1

Author(s):

Marianne E. Bronner

Keyword(s):

Mathematical Modeling ◽

Cell Migration ◽

Neural Crest ◽

Neural Crest Cells ◽

Collective Cell Migration ◽

Promote Cell Migration ◽

Neural Crest Migration ◽

Physical Boundary

Collective cell migration is a common feature in both embryogenesis and metastasis. By coupling studies of neural crest migration in vivo and in vitro with mathematical modeling, Szabó et al. (2016, J. Cell Biol., http://dx.doi.org/10.1083/jcb.201602083) demonstrate that the proteoglycan versican forms a physical boundary that constrains neural crest cells to discrete streams, in turn facilitating their migration.

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Migration and differentiation of neural crest cells and their derivatives : in vivo and in vitro studies on the early development of the avian peripheral nervous system

Reproduction Nutrition Development ◽

10.1051/rnd:19820201 ◽

1982 ◽

Vol 22 (1B) ◽

pp. 153-162 ◽

Cited By ~ 4

Author(s):

Catherine ZILLER ◽

J. SMITH

Keyword(s):

Nervous System ◽

Neural Crest ◽

Peripheral Nervous System ◽

Early Development ◽

Neural Crest Cells ◽

In Vitro Studies

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Neural crest cells bulldoze through the microenvironment using Aquaporin-1 to stabilize filopodia

10.1101/719666 ◽

2019 ◽

Cited By ~ 1

Author(s):

Rebecca McLennan ◽

Mary C. McKinney ◽

Jessica M. Teddy ◽

Jason A. Morrison ◽

Jennifer C. Kasemeier-Kulesa ◽

...

Keyword(s):

Neural Crest ◽

Protein Function ◽

Water Channel ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Aquaporin 1 ◽

Guidance Receptors ◽

Cranial Neural Crest Cells

ABSTRACTNeural crest migration requires cells to move through an environment filled with dense extracellular matrix and mesoderm to reach targets throughout the vertebrate embryo. Here, we use high-resolution microscopy, computational modeling, and in vitro and in vivo cell invasion assays to investigate the function of Aquaporin-1 (AQP-1) signaling. We find that migrating lead cranial neural crest cells express AQP-1 mRNA and protein, implicating a biological role for water channel protein function during invasion. Differential AQP-1 levels affect neural crest cell speed, direction, and the length and stability of cell filopodia. Further, AQP-1 enhances matrix metalloprotease (MMP) activity and colocalizes with phosphorylated focal adhesion kinases (pFAK). Co-localization of AQP-1 expression with EphB guidance receptors in the same migrating neural crest cells raises novel implications for the concept of guided bulldozing by lead cells during migration.

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Dual function of Slit2 in repulsion and enhanced migration of trunk, but not vagal, neural crest cells

The Journal of Cell Biology ◽

10.1083/jcb.200301041 ◽

2003 ◽

Vol 162 (2) ◽

pp. 269-279 ◽

Cited By ~ 72

Author(s):

Maria Elena De Bellard ◽

Yi Rao ◽

Marianne Bronner-Fraser

Keyword(s):

Neural Crest ◽

Neural Crest Cells ◽

Dual Function ◽

In Vitro Experiments ◽

Enteric Ganglia ◽

Robo Receptors ◽

Trunk Neural Crest ◽

Differential Ability

Neural crest precursors to the autonomic nervous system form different derivatives depending upon their axial level of origin; for example, vagal, but not trunk, neural crest cells form the enteric ganglia of the gut. Here, we show that Slit2 is expressed at the entrance of the gut, which is selectively invaded by vagal, but not trunk, neural crest. Accordingly, only trunk neural crest cells express Robo receptors. In vivo and in vitro experiments demonstrate that trunk, not vagal, crest cells avoid cells or cell membranes expressing Slit2, thereby contributing to the differential ability of neural crest populations to invade and innervate the gut. Conversely, exposure to soluble Slit2 significantly increases the distance traversed by trunk neural crest cells. These results suggest that Slit2 can act bifunctionally, both repulsing and stimulating the motility of trunk neural crest cells.

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