Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut

Enteric neural crest cells (NCCs) migrate and colonize the entire gut and proliferate and differentiate into neurons and glia of the enteric nervous system in vertebrate embryos. We have investigated the mitogenic and morphogenic functions of Sonic hedgehog (Shh) on enteric NCCs in cell and organ culture. Enteric NCCs expressed Shh receptor Patched and transcripts encoding the Shh signal transducer (Gli1). Shh promoted the proliferation and inhibited the differentiation of NCCs. The pro-neurogenic effect of glial cell line–derived neurotrophic factor (GDNF) on NCCs was abolished by Shh. In gut explants, NCCs migrated from the explants onto the adjacent substratum if GDNF was added, whereas addition of Shh abolished this migration. Neuronal differentiation and coalescence of neural crest–derived cells into myenteric plexuses in explants was repressed by the addition of Shh. Our data suggest that Shh controls the proliferation and differentiation of NCCs and modulates the responsiveness of NCCs toward GDNF inductions.

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Sonic hedgehog restricts adhesion and migration of neural crest cells independently of the Patched- Smoothened-Gli signaling pathway

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.221108698 ◽

2001 ◽

Vol 98 (22) ◽

pp. 12521-12526 ◽

Cited By ~ 62

Author(s):

S. Testaz ◽

A. Jarov ◽

K. P. Williams ◽

L. E. Ling ◽

V. E. Koteliansky ◽

...

Keyword(s):

Neural Crest ◽

Signaling Pathway ◽

Sonic Hedgehog ◽

Neural Crest Cells ◽

And Migration

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Migratory Neural Crest Cells Phagocytose Cellular Debris in the Developing Nervous System

SSRN Electronic Journal ◽

10.2139/ssrn.3380256 ◽

2019 ◽

Author(s):

Yunlu Zhu ◽

Samantha C. Crowley ◽

Andrew J. Latimer ◽

Gwendolyn M. Lewis ◽

Rebecca Nash ◽

...

Keyword(s):

Nervous System ◽

Neural Crest ◽

Neural Crest Cells ◽

Cellular Debris ◽

Developing Nervous System

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Neural crest cells and skeletogenesis in vertebrate embryos

The Histochemical Journal ◽

10.1007/bf01002715 ◽

1981 ◽

Vol 13 (4) ◽

pp. 631-642 ◽

Cited By ~ 19

Author(s):

Peter Thorogood

Keyword(s):

Neural Crest ◽

Neural Crest Cells ◽

Vertebrate Embryos

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Vitamin E is Necessary to Protect Neural Crest Cells in Developing Zebrafish Embryos

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_025 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1209-1209

Author(s):

Brian Head ◽

Jane La Du ◽

Robyn Tanguay ◽

Chrissa Kioussi ◽

Maret Traber

Keyword(s):

Nervous System ◽

Vitamin E ◽

Neural Crest ◽

System Development ◽

Neural Crest Cells ◽

Nervous System Development ◽

Neural Plate ◽

Zebrafish Embryos ◽

Normal Brain ◽

Collagen Formation

Abstract Objectives Vitamin E (VitE) deficiency causes vertebrate embryonic lethality. The alpha-tocopherol transfer protein (Ttpa) likely regulates VitE distribution in the early zebrafish embryo because Ttpa knockdown causes impaired nervous system development and embryonic death by 15–18 hours post-fertilization (hpf). We propose that VitE is necessary for normal brain and peripheral nervous system development. Methods Zebrafish embryos are obtained from adults fed either VitE sufficient (E+) or deficient (E–) diets for at least 80 days. Embryos at 12 and 24 hpf are subjected to RNA whole mount in situ hybridization (WISH). RNA is also collected from embryos at 12, 18 and 24 hpf for RT-qPCR of specific targets. Results At 12 hpf, the midbrain-hindbrain boundary and otic placodes are malformed in E– embryos, as shown by Pax2a expression. Similarly, Sox10 expression shows that E– embryos lack clear neural plate borders. Nonetheless, in 12 hpf E + and E− embryos Ttpa is localized similarly throughout the nervous system. Pax2a expression initiates collagen formation in the developing notochord. Collagen genes, col2a1a and col9a2, expression patterns showed abnormal notochord structures in 24 hpf E– embryos. At 24 hpf in E + embryos, Sox10 expressing-neural crest cells are localized both in the central nervous system and dorsal root ganglia (DRG), while the Sox10 signal is diminished in E– embryos in both the DRG and early enteric nervous system. At 24 hpf, Ttpa expression outlines the brain ventricle borders; critically E– embryos show reduced Ttpa signal and impaired ventricle closing. Gene expression by qPCR will be used to confirm these results. Conclusions This VitE deficient embryo model suggests that the carefully programmed development of the nervous system is distorted due to lack of adequate VitE. Thus, Ttpa and VitE are critical molecules for neural plate and neural tube formation, and neural crest cell migration. Funding Sources The authors received no specific funding for this work.

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Enteric nervous system formation: disproportionate stochastic clonal expansion of a few initiating vagal neural crest cells

Mechanisms of Development ◽

10.1016/j.mod.2017.04.061 ◽

2017 ◽

Vol 145 ◽

pp. S40-S41

Author(s):

Donald Newgreen ◽

Dongcheng Zhang ◽

James Osborne ◽

Bevan Cheeseman ◽

Benjamin Binder ◽

...

Keyword(s):

Nervous System ◽

Neural Crest ◽

Enteric Nervous System ◽

Neural Crest Cells ◽

Clonal Expansion ◽

System Formation

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A pluri- és multipotencia határán: a ganglionléc őssejtjei

Orvosi Hetilap ◽

10.1556/650.2015.30271 ◽

2015 ◽

Vol 156 (42) ◽

pp. 1683-1694

Author(s):

Gyöngyi Kudlik ◽

Zsolt Matula ◽

Tamás Kovács ◽

S. Veronika Urbán ◽

Ferenc Uher

Keyword(s):

Stem Cells ◽

Nervous System ◽

Neural Crest ◽

Cell Biology ◽

Pigment Cells ◽

Stem Cell Biology ◽

Vertebrate Embryos ◽

Derivatives Of ◽

Review Current ◽

Migratory Cell

The neural crest is a transient, multipotent, migratory cell population that is unique to vertebrate embryos and gives rise to many derivatives, ranging from the neuronal and glial components of the peripheral nervous system to the ectomesenchymal derivatives of the craniofacial area and pigment cells in the skin. Intriguingly, the neural crest derived stem cells are not only present in the embryonic neural crest, but also in their target tissues in the fetus and adult. These postmigratory stem cells, at least partially, resemble their multipotency. Moreover, fully differentiated neural crest-derived cells such as Schwann cells and melanocytes are able to dedifferentiate into stem-like progenitors. Here the authors review current understanding of this unique plasticity and its potential application in stem cell biology as well as in regenerative medicine. Orv. Hetil., 2015, 156(42), 1683–1694.

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Neural crest cell migration: requirements for exogenous fibronectin and high cell density.

The Journal of Cell Biology ◽

10.1083/jcb.96.2.462 ◽

1983 ◽

Vol 96 (2) ◽

pp. 462-473 ◽

Cited By ~ 258

Author(s):

R A Rovasio ◽

A Delouvee ◽

K M Yamada ◽

R Timpl ◽

J P Thiery

Keyword(s):

Cell Adhesion ◽

Neural Crest ◽

Type I Collagen ◽

Neural Crest Cell ◽

Neural Crest Cells ◽

Type I ◽

Cell Adhesion And Migration ◽

And Migration ◽

Crest Cell

Cells of the neural crest participate in a major class of cell migratory events during embryonic development. From indirect evidence, it has been suggested that fibronectin (FN) might be involved in these events. We have directly tested the role of FN in neural crest cell adhesion and migration using several in vitro model systems. Avian trunk neural crest cells adhered readily to purified plasma FN substrates and to extracellular matrices containing cellular FN. Their adhesion was inhibited by antibodies to a cell-binding fragment of FN. In contrast, these cells did not adhere to glass, type I collagen, or to bovine serum albumin in the absence of FN. Neural crest cell adhesion to laminin (LN) was significantly less than to FN; however, culturing of crest cells under conditions producing an epithelioid phenotype resulted in cells that could bind equally as well to LN as to FN. The migration of neural crest cells appeared to depend on both the substrate and the extent of cell interactions. Cells migrated substantially more rapidly on FN than on LN or type I collagen substrates; if provided a choice between stripes of FN and glass or LN, cells migrated preferentially on the FN. Migration was inhibited by antibodies against the cell-binding region of FN, and the inhibition could be reversed by a subsequent addition of exogenous FN. However, the migration on FN was random and displayed little persistence of direction unless cells were at high densities that permitted frequent contacts. The in vitro rate of migration of cells on FN-containing matrices was 50 microns/h, similar to their migration rates along the narrow regions of FN-containing extracellular matrix in migratory pathways in vivo. These results indicate that FN is important for neural crest cell adhesion and migration and that the high cell densities of neural crest cells in the transient, narrow migratory pathways found in the embryo are necessary for effective directional migration.

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