Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells.

Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047 Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 06/2003; 100(10):5828-33. DOI: 10.1073/pnas.1037282100
Source: PubMed

ABSTRACT To understand the range of competence of embryonic stem (ES) cell-derived neural precursors, we have examined in vitro differentiation of mouse and primate ES cells into the dorsal- (neural crest) and ventralmost (floor plate) cells of the neural axis. Stromal cell-derived inducing activity (SDIA; accumulated on PA6 stromal cells) induces cocultured ES cells to differentiate into rostral CNS tissues containing both ventral and dorsal cells. Although early exposure of SDIA-treated ES cells to bone morphogenetic protein (BMP)4 suppresses neural differentiation and promotes epidermogenesis, late BMP4 exposure after the fourth day of coculture causes differentiation of neural crest cells and dorsalmost CNS cells, with autonomic system and sensory lineages induced preferentially by high and low BMP4 concentrations, respectively. In contrast, Sonic hedgehog (Shh) suppresses differentiation of neural crest lineages and promotes that of ventral CNS tissues such as motor neurons. Notably, high concentrations of Shh efficiently promote differentiation of HNF3beta(+) floor plate cells with axonal guidance activities. Thus, SDIA-treated ES cells generate naive precursors that have the competence of differentiating into the "full" dorsal-ventral range of neuroectodermal derivatives in response to patterning signals.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The developmental fate of the multipotent neural crest (NC) is determined along with the neural axis in which NC cells are generated. Only the cranial NC can differentiate to mesectodermal derivatives such as osteoblasts, chondrocytes, and adipocytes in vivo. Here, we attempted to selectively differentiate mouse embryonic stem (ES) cells into cranial NC stem cells and propagate them to explore their developmental potential to differentiate into mesectodermal derivatives. Using aggregation cultures in feeder- and serum-free neural induction medium (NIM) without serum replacement and L-glutamine, we obtained NIM neurospheres composed of neuroepithelium. The NIM neurospheres expressed the rostral markers Otx1 and Otx2, but not non-rostral markers Hoxb4, Hoxb9, Lbx1, and TH, which characterize cranial neurospheres. Subsequently, AP2α, Sox9, p75, Snail, Slug, and Twist-positive NC cells were differentiated in 4-day adhesion cultures of cranial neurospheres. Additionally, sphere clusters in adhesion cultures were differentiated into osteoblast while migrating cells were not. By taking advantage of the sphere-formation capability, we isolated and propagated NC stem cells from the sphere clusters and confirmed their multipotency. NC stem cells expressed NC and stem cell markers, and maintained differentiation potency in the NC derivatives. These results show that cranial NC stem cells were obtained reproducibly and efficiently without special inducing factors, gene transfection or fluorescence-activated cell sorting (FACS) selection.
    Stem Cells and Development 08/2014; · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Members of the transforming growth factor-β (TGF-β) family have been implicated in embryogenesis as well as inthe determination of the cell fatesofmouse and human embryonic stem (ES) cells, which are characterized by their self-renewal and pluripotency.The cellular responses to TGF-βfamilysignals are divergent depending on the cellular context and local environment. TGF-β family signals play critical roles both in the maintenance of the pluripotent state of ES cells by inducing the expression of Nanog, Oct4, and Sox2, and in their differentiation into various cell types by regulating the expression of master regulatory genes. Moreover, multiple lines of evidence have suggested the importance of TGF-βfamilysignalsin establishing induced pluripotent stem (iPS) cells. Since ES and iPScells have great potential for applications in regenerative medicine, it is criticalto figure out the mechanisms underlying their self-renewal, pluripotency, and differentiation.Here, wediscuss the roles of TGF-β familyligands and their downstreamsignaling molecules,Smad proteins, in the maintenance of thepluripotency and lineage specification of mouse and human ES and iPScells.
    Seminars in Cell and Developmental Biology 06/2014; · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The neural crest is the name given to the strip of cells at the junction between neural and epidermal ectoderm in neurula-stage vertebrate embryos, which is later brought to the dorsal neural tube as the neural folds elevate. The neural crest is a heterogeneous and multipotent progenitor cell population whose cells undergo EMT then extensively and accurately migrate throughout the embryo. Neural crest cells contribute to nearly every organ system in the body, with derivatives of neuronal, glial, neuroendocrine, pigment, and also mesodermal lineages. This breadth of developmental capacity has led to the neural crest being termed the fourth germ layer. The neural crest has occupied a prominent place in developmental biology, due to its exaggerated migratory morphogenesis and its remarkably wide developmental potential. As such, neural crest cells have become an attractive model for developmental biologists for studying these processes. Problems in neural crest development cause a number of human syndromes and birth defects known collectively as neurocristopathies; these include Treacher Collins syndrome, Hirschsprung disease, and 22q11.2 deletion syndromes. Tumors in the neural crest lineage are also of clinical importance, including the aggressive melanoma and neuroblastoma types. These clinical aspects have drawn attention to the selection or creation of neural crest progenitor cells, particularly of human origin, for studying pathologies of the neural crest at the cellular level, and also for possible cell therapeutics. The versatility of the neural crest lends itself to interlinked research, spanning basic developmental biology, birth defect research, oncology, and stem/progenitor cell biology and therapy. Birth Defects Research (Part C), 2014. © 2014 Wiley Periodicals, Inc.
    Birth Defects Research Part C Embryo Today Reviews 09/2014; · 4.44 Impact Factor

Full-text (2 Sources)

Available from
Jun 1, 2014