scholarly journals Identification of bipotent progenitors that give rise to myogenic and connective tissues in mouse

2021 ◽  
Author(s):  
Alexandre Grimaldi ◽  
Glenda Evangelina Comai ◽  
Sebastien Mella ◽  
Shahragim Tajbakhsh

How distinct cell fates are manifested by direct lineage ancestry from bipotent progenitors, or by specification of individual cell types within a field of cells is a key question for understanding the emergence of tissues. The interplay between skeletal muscle progenitors and associated connective tissues cells provides a model for examining how muscle functional units are established. Most craniofacial structures originate from the vertebrate-specific neural crest cells except in the dorsal portion of the head, where they arise from cranial mesoderm. Here, using multiple lineage-traced single cell RNAseq, advanced computational methods and in situ analyses, we identify Myf5+ bipotent progenitors that give rise to both muscle and juxtaposed connective tissue. Following this bifurcation, muscle and connective tissue cells retain complementary signalling features and maintain spatial proximity. Interruption of upstream myogenic identity shifts muscle progenitors to a connective tissue fate. Interestingly, Myf5-derived connective tissue cells, which adopt a novel regulatory signature, were not observed in ventral craniofacial structures that are colonised by neural crest cells. Therefore, we propose that an ancestral program gives rise to bifated muscle and connective tissue cells in skeletal muscles that are deprived of neural crest.

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 925-934 ◽  
Author(s):  
L.C. Smith-Thomas ◽  
A.R. Johnson ◽  
J.W. Fawcett

Amongst the many cell types that differentiate from migratory neural crest cells are the Schwann cells of the peripheral nervous system. While it has been demonstrated that Schwann cells will not fully differentiate unless in contact with neurons, the factors that cause neural crest cells to enter the differentiative pathway that leads to Schwann cells are unknown. In a previous paper (Development 105: 251, 1989), we have demonstrated that a proportion of morphologically undifferentiated neural crest cells express the Schwann cell markers 217c and NGF receptor, and later, as they acquire the bipolar morphology typical of Schwann cells in culture, express S-100 and laminin. In the present study, we have grown axons from embryonic retina on neural crest cultures to see whether this has an effect on the differentiation of neural crest cells into Schwann cells. After 4 to 6 days of co-culture, many more cells had acquired bipolar morphology and S-100 staining than in controls with no retinal explant, and most of these cells were within 200 microns of an axon, though not necessarily in contact with axons. However, the number of cells expressing the earliest Schwann cell markers 217c and NGF receptor was not affected by the presence of axons. We conclude that axons produce a factor, which is probably diffusible, and which makes immature Schwann cells differentiate. The factor does not, however, influence the entry of neural crest cells into the earliest stages of the Schwann cell differentiative pathway.


Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 421-433
Author(s):  
J.L. Duband ◽  
J.P. Thiery

Neural crest cells express different adhesion modes at each phase of their development starting with their separation from the neural tube, followed by migration along definite pathways throughout the embryo, and finally to settlement and differentiation in elected embryonic regions. In order to determine possible changes in the cytoskeleton organization and function during these processes, we have studied the in situ distribution of two major cytoskeleton-associated elements involved in the membrane anchorage of actin microfilaments, i.e. vinculin and talin, during the ontogeny of the neural crest and its derivatives in the avian embryo. Prior to emigration, neural crest cells exhibited both vinculin and talin at levels similar to the neighbouring neural epithelial cells, and this expression apparently did not change as cells became endowed with migratory properties. However, vinculin became selectively enhanced in neural crest cells as they further migrated towards their final destination. This increase in vinculin amount was particularly striking in vagal and truncal neural crest cells entering cellular environments, such as the sclerotome and the gut mesenchyme. Talin was also expressed by neural crest cells but, in contrast to vinculin, staining was not conspicuous compared to neighbouring mesenchymal cells. High levels of vinculin persisted throughout embryogenesis in almost all neural derivatives of the neural crest, including the autonomous and sensory ganglia and Schwann cells along the peripheral nerves. In contrast, the non-neural derivatives of the neural crest rapidly lost their prominent vinculin staining after migration. The pattern of talin in the progeny of the neural crest was complex and varied with the cell types: for example, some cranial sensory ganglia expressed high amounts of the molecule whereas autonomic ganglia were nearly devoid of it. Our results suggest that (i) vinculin and talin may follow independent regulatory patterns within the same cell population, (ii) the level of expression of vinculin and talin in neural crest cells may be consistent with the rapid, constant modulations of their adhesive properties, and (iii) the expression patterns of the two molecules may also be correlated with the genesis of the peripheral nervous system.


2018 ◽  
Vol 52 (1) ◽  
pp. 43-63 ◽  
Author(s):  
András Szabó ◽  
Roberto Mayor

Neural crest cells are a transient embryonic cell population that migrate collectively to various locations throughout the embryo to contribute a number of cell types to several organs. After induction, the neural crest delaminates and undergoes an epithelial-to-mesenchymal transition before migrating through intricate yet characteristic paths. The neural crest exhibits a variety of migratory behaviors ranging from sheet-like mass migration in the cephalic regions to chain migration in the trunk. During their journey, neural crest cells rely on a range of signals both from their environment and within the migrating population for navigating through the embryo as a collective. Here we review these interactions and mechanisms, including chemotactic cues of neural crest cells’ migration.


2000 ◽  
Vol 20 (9) ◽  
pp. 3004-3014 ◽  
Author(s):  
Matthew L. Bilodeau ◽  
Theresa Boulineau ◽  
Ronald L. Hullinger ◽  
Ourania M. Andrisani

ABSTRACT Cells of the vertebrate neural crest (crest cells) are an invaluable model system to address cell fate specification. Crest cells are amenable to tissue culture, and they differentiate to a variety of neuronal and nonneuronal cell types. Earlier studies have determined that bone morphogenetic proteins (BMP-2, -4, and -7) and agents that elevate intracellular cyclic AMP (cAMP) stimulate the development of the sympathoadrenal (SA, adrenergic) lineage in neural crest cultures. To investigate whether interactive mechanisms between signaling pathways influence crest cell differentiation, we characterized the combinatorial effects of BMP-2 and cAMP-elevating agents on the development of quail trunk neural crest cells in primary culture. We report that the cAMP signaling pathway modulates both positive and negative signals influencing the development of SA cells. Specifically, we show that moderate activation of cAMP signaling promotes, in synergy with BMP-2, SA cell development and the expression of the SA lineage-determining gene Phox2a. By contrast, robust activation of cAMP signaling opposes, even in the presence of BMP-2, SA cell development and the expression of the SA lineage-determining ASH-1 and Phox2 genes. We conclude that cAMP signaling acts as a bimodal regulator of SA cell development in neural crest cultures.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Debadrita Bhattacharya ◽  
Megan Rothstein ◽  
Ana Paula Azambuja ◽  
Marcos Simoes-Costa

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.


Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 857-866 ◽  
Author(s):  
G.N. Serbedzija ◽  
S. Burgan ◽  
S.E. Fraser ◽  
M. Bronner-Fraser

We have used the vital dye, DiI, to analyze the contribution of sacral neural crest cells to the enteric nervous system in chick and mouse embryos. In order to label premigratory sacral neural crest cells selectively, DiI was injected into the lumen of the neural tube at the level of the hindlimb. In chick embryos, DiI injections made prior to stage 19 resulted in labelled cells in the gut, which had emerged from the neural tube adjacent to somites 29–37. In mouse embryos, neural crest cells emigrated from the sacral neural tube between E9 and E9.5. In both chick and mouse embryos, DiI-labelled cells were observed in the rostral half of the somitic sclerotome, around the dorsal aorta, in the mesentery surrounding the gut, as well as within the epithelium of the gut. Mouse embryos, however, contained consistently fewer labelled cells than chick embryos. DiI-labelled cells first were observed in the rostral and dorsal portion of the gut. Paralleling the maturation of the embryo, there was a rostral-to-caudal sequence in which neural crest cells populated the gut at the sacral level. In addition, neural crest cells appeared within the gut in a dorsal-to-ventral sequence, suggesting that the cells entered the gut dorsally and moved progressively ventrally. The present results resolve a long-standing discrepancy in the literature by demonstrating that sacral neural crest cells in both the chick and mouse contribute to the enteric nervous system in the postumbilical gut.


Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 913-920 ◽  
Author(s):  
S.E. Fraser ◽  
M. Bronner-Fraser

Trunk neural crest cells migrate extensively and give rise to diverse cell types, including cells of the sensory and autonomic nervous systems. Previously, we demonstrated that many premigratory trunk neural crest cells give rise to descendants with distinct phenotypes in multiple neural crest derivatives. The results are consistent with the idea that neural crest cells are multipotent prior to their emigration from the neural tube and become restricted in phenotype after leaving the neural tube either during their migration or at their sites of localization. Here, we test the developmental potential of migrating trunk neural crest cells by microinjecting a vital dye, lysinated rhodamine dextran (LRD), into individual cells as they migrate through the somite. By two days after injection, the LRD-labelled clones contained from 2 to 67 cells, which were distributed unilaterally in all embryos. Most clones were confined to a single segment, though a few contributed to sympathetic ganglia over two segments. A majority of the clones gave rise to cells in multiple neural crest derivatives. Individual migrating neural crest cells gave rise to both sensory and sympathetic neurons (neurofilament-positive), as well as cells with the morphological characteristics of Schwann cells, and other non-neuronal cells (both neurofilament-negative). Even those clones contributing to only one neural crest derivative often contained both neurofilament-positive and neurofilament-negative cells. Our data demonstrate that migrating trunk neural crest cells can be multipotent, giving rise to cells in multiple neural crest derivatives, and contributing to both neuronal and non-neuronal elements within a given derivative.(ABSTRACT TRUNCATED AT 250 WORDS)


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Thomas JR Frith ◽  
Ilaria Granata ◽  
Matthew Wind ◽  
Erin Stout ◽  
Oliver Thompson ◽  
...  

The neural crest (NC) is a multipotent embryonic cell population that generates distinct cell types in an axial position-dependent manner. The production of NC cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology. However, the origin of human trunk NC remains undefined and current in vitro differentiation strategies induce only a modest yield of trunk NC cells. Here we show that hPSC-derived axial progenitors, the posteriorly-located drivers of embryonic axis elongation, give rise to trunk NC cells and their derivatives. Moreover, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities in vitro. Collectively, our findings indicate that there are two routes toward a human post-cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas trunk NC arises within a pool of posterior axial progenitors.


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