The control of pigment cell pattern formation in the California newt, Taricha torosa

Development ◽  
1986 ◽  
Vol 97 (1) ◽  
pp. 141-168
Author(s):  
R. P. Tucker ◽  
C. A. Erickson

Neural crest-derived pigment cells form species-specific patterns of pigmentation in amphibian embryos. We have characterized the appearance and changes in pigment cell distribution in the embryos of the California newt, Taricha torosa. Black melanophores first appear scattered over the surface of the somites intermingled with yellow xanthophores in stage 34/35 embryos. The melanophores then migrate either dorsally to form a dorsal stripe at the apex of the somites or ventrally along the intersomitic furrows to form a midbody stripe at the somite—lateral plate mesoderm border. Xanthophores remain between the two melanophore stripes and are also found in the dorsal fin and head. The formation of the dorsal stripe coincides with a change in melanophore tissue affinity from the surface of the somites to the subectodermal extracellular matrix (ECM). The latter substratum is the location of the cue used to organize the dorsal stripe. In addition, melanophores become elongate and highly arborized, which would allow them to extend to the region where the dorsal stripe forms. In contrast, xanthophores do not form long processes in vitro. This suggests that the ability of melanophores but not xanthophores to search for a cue at the apex of the somites may account in part for the segregation of these cells types. Melanophores and xanthophores are trapped to form the midbody stripe by the pronephric duct, which is located just beneath the ectoderm at the bases of the intersomitic furrows. Ablation of the duct prevents formation of the midbody stripe, although melanophores and xanthophores still fail to migrate ventrally over the lateral plate mesoderm. Melanophores grafted to the ventral midline fail to leave the confines of the donor tissue. This suggests that a factor in the lateral plate mesoderm in addition to the pronephric duct is inhibiting further ventral migration. There is no gross morphological difference in the organization of the subectodermal ECM dorsal and ventral to the pronephric duct as revealed by alcian blue, ruthenium red and staining with antibodies to fibronectin. We also conclude that the directed dispersal of the neural crest into the space between the somites and ectoderm is due to contact inhibition of cell movement, since T. torosa neural crest cells demonstrate contact inhibition in vitro and there are enough cells in the lateral migratory spaces to make contact events likely during dispersal.

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 411-423 ◽  
Author(s):  
T.P. Rothman ◽  
N.M. Le Douarin ◽  
J.C. Fontaine-Perus ◽  
M.D. Gershon

The technique of back-transplantation was used to investigate the developmental potential of neural crest-derived cells that have migrated to and colonized the avian bowel. Segments of quail bowel (removed at E4) were grafted between the somites and neural tube of younger (E2) chick host embryos. Grafts were placed at a truncal level, adjacent to somites 14–24. Initial experiments, done in vitro, confirmed that crest-derived cells are capable of migrating out of segments of foregut explanted at E4. The foregut, which at E4 has been colonized by cells derived from the vagal crest, served as the donor tissue. Comparative observations were made following grafts of control tissues, which included hindgut, lung primordia, mesonephros and limb bud. Additional experiments were done with chimeric bowel in which only the crest-derived cells were of quail origin. Targets in the host embryos colonized by crest-derived cells from the foregut grafts included the neural tube, spinal roots and ganglia, peripheral nerves, sympathetic ganglia and the adrenals, but not the gut. Donor cells in these target organs were immunostained by the monoclonal antibody, NC-1, indicating that they were crest-derived and developing along neural or glial lineages. Some of the crest-derived cells (NC-1-immunoreactive) that left the bowel and reached sympathetic ganglia, but not peripheral nerves or dorsal root ganglia, co-expressed tyrosine hydroxylase immunoreactivity, a neural characteristic never expressed by crest-derived cells in the avian gut. None of the cells leaving enteric back-grafts produced pigment. Cells of mesodermal origin were also found to leave donor explants and aggregate in dermis and feather germs near the grafts. These observations indicate that crest-derived cells, having previously migrated to the bowel, retain the ability to migrate to distant sites in a younger embryo. The routes taken by these cells appear to reflect, not their previous migratory experience, but the level of the host embryo into which the graft is placed. Some of the population of crest-derived cells that leave the back-transplanted gut remain capable of expressing phenotypes that they do not express within the bowel in situ, but which are appropriate for the site in the host embryo to which they migrate.


Author(s):  
Gemma Sutton ◽  
Robert N. Kelsh ◽  
Steffen Scholpp

The neural crest (NC) is a multipotent cell population in vertebrate embryos with extraordinary migratory capacity. The NC is crucial for vertebrate development and forms a myriad of cell derivatives throughout the body, including pigment cells, neuronal cells of the peripheral nervous system, cardiomyocytes and skeletogenic cells in craniofacial tissue. NC induction occurs at the end of gastrulation when the multipotent population of NC progenitors emerges in the ectodermal germ layer in the neural plate border region. In the process of NC fate specification, fate-specific markers are expressed in multipotent progenitors, which subsequently adopt a specific fate. Thus, NC cells delaminate from the neural plate border and migrate extensively throughout the embryo until they differentiate into various cell derivatives. Multiple signalling pathways regulate the processes of NC induction and specification. This review explores the ongoing role of the Wnt/β-catenin signalling pathway during NC development, focusing on research undertaken in the Teleost model organism, zebrafish (Danio rerio). We discuss the function of the Wnt/β-catenin signalling pathway in inducing the NC within the neural plate border and the specification of melanocytes from the NC. The current understanding of NC development suggests a continual role of Wnt/β-catenin signalling in activating and maintaining the gene regulatory network during NC induction and pigment cell specification. We relate this to emerging models and hypotheses on NC fate restriction. Finally, we highlight the ongoing challenges facing NC research, current gaps in knowledge, and this field’s potential future directions.


2019 ◽  
Author(s):  
Alec K. Gramann ◽  
Arvind M. Venkatesan ◽  
Melissa Guerin ◽  
Craig J. Ceol

AbstractPreventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand GDF6 as a novel melanoma oncogene showed GDF6-activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for GDF6 orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand gdf6a, a zebrafish ortholog of human GDF6, during the development of melanocytes from the neural crest. We establish that the loss of gdf6a or inhibition of BMP signaling during neural crest development disrupts normal pigment cell development, leading to an increase in the number of melanocytes and a corresponding decrease in iridophores, another neural crest-derived pigment cell type in zebrafish. This shift occurs as pigment cells arise from the neural crest and depends on mitfa, an ortholog of MITF, a key regulator of melanocyte development that is also targeted by oncogenic BMP signaling. Together, these results indicate that the oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.


Development ◽  
1978 ◽  
Vol 48 (1) ◽  
pp. 1-21
Author(s):  
D. J. Pritchard ◽  
R. M. Clayton ◽  
D. I. De Pomerai

The in vitro transdifferentiation of chicken embryo neural retina into pigment epithelium and lens cells was investigated under a variety of experimental conditions. Our findings suggest that some aspects of the phenomena are a function of medium composition and volume, whereas others depend upon conditions which develop during culture growth. Before melanin is visible, potential pigment cells are recognized as foci within epithelialsheets which remain in contact with the dish. The final area occupied by colonies of potential pigment cells is directly proportional to bicarbonate concentration. Low total medium volume also favours formation of potential pigment cells. In contrast the extent of cells other than potential pigment cells is not related to bicarbonate and is favoured when the volume of medium is large. Accumulation of melanin within the potential pigment cell colonies is suppressed when cells are crowded together. Lentoid bodies are formed from cells which are distinct from potential pigment cells and arise in crowded situations, in association with multilayering. Another type of structure superficially resembling a lentoid is derived from cell aggregates formed during the initial establishment of cultures. The survival of these ‘aggregate bodies’ is inversely related to bicarbonate concentration. Crystallin content is unrelated to lentoid numbers. The results provide the basis for a new hypothesis concerning cytodifferentiation in this system.


Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3757-3767 ◽  
Author(s):  
J.A. Lister ◽  
C.P. Robertson ◽  
T. Lepage ◽  
S.L. Johnson ◽  
D.W. Raible

We report the isolation and identification of a new mutation affecting pigment cell fate in the zebrafish neural crest. Homozygous nacre (nac(w2)) mutants lack melanophores throughout development but have increased numbers of iridophores. The non-crest-derived retinal pigment epithelium is normal, suggesting that the mutation does not affect pigment synthesis per se. Expression of early melanoblast markers is absent in nacre mutants and transplant experiments suggested a cell-autonomous function in melanophores. We show that nac(w2) is a mutation in a zebrafish gene encoding a basic helix-loop-helix/leucine zipper transcription factor related to microphthalmia (Mitf), a gene known to be required for development of eye and crest pigment cells in the mouse. Transient expression of the wild-type nacre gene restored melanophore development in nacre(−/−) embryos. Furthermore, misexpression of nacre induced the formation of ectopic melanized cells and caused defects in eye development in wild-type and mutant embryos. These results demonstrate that melanophore development in fish and mammals shares a dependence on the nacre/Mitf transcription factor, but that proper development of the retinal pigment epithelium in the fish is not nacre-dependent, suggesting an evolutionary divergence in the function of this gene.


Development ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 41-58
Author(s):  
Ruth Bellairs ◽  
P. A. Portch ◽  
E. J. Sanders

Tissue culture, time-lapse cinematographic and electron microscopic techniques have been used to study the properties of chick mesoderm at several stages of differentiation. Lateral plate, unsegmented mesoderm (segmental plate), and newly formed somites were dissected from stage-12 embryos, whilst dermo-myotomes and sclerotomes were dissected from stage-18 embryos. Each type of mesoderm was found to exhibit a characteristic pattern of behaviour. The explants from the unsegmented mesoderm, from the newly formed somites and from the older embryos could be placed in a developmental sequence; with increasing differentiation they settled and spread on the substrate more readily, whether explanted as pieces of tissue or as individual cells, and it was concluded that this implied an increased adhesion to the substrate. Similarly, with increasing differentiation, the cells segmented at a faster rate. No significant differences could be discerned in the internal structure of the different types of cells, although differences in the general shape were apparent. The lateral plate mesoderm cells, which bear some resemblances to the unsegmented mesoderm cells in the embryo, also show some morphological resemblances to them in vitro. However, the lateral plate cells had a much greater success in attaching to glass or plastic substrates. They were also found to have the highest speed of locomotion of all the tissues studied, whereas the unsegmented had the lowest. It is concluded therefore, that although cells may look similar to one another morphologically, their behaviour may differ greatly, probably because they are already partially determined.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jun Jie Tan ◽  
Jacques P. Guyette ◽  
Kenji Miki ◽  
Ling Xiao ◽  
Gurbani Kaur ◽  
...  

AbstractEpicardial formation is necessary for normal myocardial morphogenesis. Here, we show that differentiating hiPSC-derived lateral plate mesoderm with BMP4, RA and VEGF (BVR) can generate a premature form of epicardial cells (termed pre-epicardial cells, PECs) expressing WT1, TBX18, SEMA3D, and SCX within 7 days. BVR stimulation after Wnt inhibition of LPM demonstrates co-differentiation and spatial organization of PECs and cardiomyocytes (CMs) in a single 2D culture. Co-culture consolidates CMs into dense aggregates, which then form a connected beating syncytium with enhanced contractility and calcium handling; while PECs become more mature with significant upregulation of UPK1B, ITGA4, and ALDH1A2 expressions. Our study also demonstrates that PECs secrete IGF2 and stimulate CM proliferation in co-culture. Three-dimensional PEC-CM spheroid co-cultures form outer smooth muscle cell layers on cardiac micro-tissues with organized internal luminal structures. These characteristics suggest PECs could play a key role in enhancing tissue organization within engineered cardiac constructs in vitro.


Development ◽  
1962 ◽  
Vol 10 (3) ◽  
pp. 293-314
Author(s):  
Cyril V. Finnegan

Following its involution around the lateral lips of the blastopore, the potential hypomere (lateral plate mesoderm) of Urodeles undergoes a dorsal convergence, along with other portions of the mesoderm mantle and then, during neurulation, initiates an independent ventrad migration (Nieuwkoop, 1947). As the hypomere migrates ventrally, it becomes further removed from the influences shown by Yamada (1950) to emanate from the mid-dorsal axial system and its deep layer is in contact with a tissue (endoderm) which seems to be influential in the differentiation of this mesoderm (Bacon, 1945; Jacobson, 1960; Nieuwkoop, 1947, 1950; Finnegan, 1953, 1955, 1961a, 1961b). A further understanding of the postgastrula development of the trunk hypomere seemed to require information of the possible restriction, in time, of the competence of this mesoderm or, alternatively, its degree of self-differentiation within an embryonic system for in vitro observations may indicate histogenetic potencies unrelated to normal development (Finnegan, 1961a, 1961b).


Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 47-62
Author(s):  
D. J. Pritchard

Neural retina from 8- to 9-day embryo chickens was grown in long-term cell culture in an experiment to test the hpothesis that one step during the in vitro transdifferentiation of neural retina into pigment cells occurs in response to stimulation of tricarboxylic acid (TCA) cycle activity. Time-lapse photography showed that pigment-cell formation occurs through the intermediate stages of ‘undistinguished cells’, ‘pavement epithelium’ and ‘potential pigment cells’. Mitosis of undistinguished cells to pavement epithelium was proportional to malonate over most of the tested range of concentrations and was inhibited by succinate, which respectively depress and stimulate the TCA cycle. Conversely mitosis of pavement epithelium to potential pigment cells occurred in proportion to succinate concentration over most of the tested range and was inhibited by malonate, in support of the hypothesis under test. Melanin synthesis begins in a minority of ‘pigment leader cells’ uniquely stimulated by the lowest concentration of malonate, although higher concentrations blocked pigment synthesis in all cell types. The pigment leader cells appear to act as centres of influence upon neighbouring potential pigment cells, which subsequently also beome pigmented. Lactate inhibited most or all of the steps in formation of pigment epithelium. Between three and five mitoses occur in the production of pigment cells, whereas multilayers and lentoid bodies seem to be formed by expansion of undistinguished cells, probably without mitosis. The observations lead to a general theory that metaplastic conversion between cell types in eye tissues may require the physical isolation of overtly differentiated, multipotent cells from ‘leader’ cells which normally hold them in physiological subjugation.


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