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

Fu M, Lui VC, Sham MH, Pachnis V, Tam PK - J. Cell Biol. (2004)

Bottom Line: 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.Our data suggest that Shh controls the proliferation and differentiation of NCCs and modulates the responsiveness of NCCs toward GDNF inductions.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The University of Hong Kong, 21 Sassoon Rd., Pokfulam, Hong Kong, HKSAR China.

ABSTRACT
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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Related in: MedlinePlus

Shh restricts the migration of NCCs. Migratory cells on the filter from explants cultured for 3 d in the presence of GDNF (A–C) or GDNF + Shh (D–F) were stained for TUJ1 (A and D, green), Ret (B and E, red), or PH3 (C and F, red). PH3+ cells and total number of cells on the membrane in each treatment were counted (n, number of explants in each treatment); and percentage of PH3+ cells was calculated and tabulated as shown.
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fig6: Shh restricts the migration of NCCs. Migratory cells on the filter from explants cultured for 3 d in the presence of GDNF (A–C) or GDNF + Shh (D–F) were stained for TUJ1 (A and D, green), Ret (B and E, red), or PH3 (C and F, red). PH3+ cells and total number of cells on the membrane in each treatment were counted (n, number of explants in each treatment); and percentage of PH3+ cells was calculated and tabulated as shown.

Mentions: The migratory cells that were collected from the membrane for counting expressed Ret and TUJ1, confirming that these cells were derivatives of enteric NCCs (Fig. 5 N). Few NCCs migrated out of the explants in the absence of GDNF. Addition of Shh reduced the number of migratory NCCs by half, as compared with those treated with GDNF alone (Fig. 5 N; P = 0.003; t test). NCCs on the membrane had differentiated into neurons as they expressed TUJ1 (Fig. 6, A and D). However, some of these TUJ1+ cells were still proliferating as revealed by PH3 immunoreactivity (Fig. 6, A–F). The proportion of PH3+ cells on the membrane was similar between the cultures with or without Shh, indicating that the proliferation of cells on the membrane was comparable in these cultures (P > 0.05; t test). This finding suggested that the variable numbers of cells on the membrane in various treatments was not the consequence of different proliferation of migratory cells on the membrane. In other words, the numbers of cells on the membrane could reflect the number of migratory NCCs from the explants in response to different factors.


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

Fu M, Lui VC, Sham MH, Pachnis V, Tam PK - J. Cell Biol. (2004)

Shh restricts the migration of NCCs. Migratory cells on the filter from explants cultured for 3 d in the presence of GDNF (A–C) or GDNF + Shh (D–F) were stained for TUJ1 (A and D, green), Ret (B and E, red), or PH3 (C and F, red). PH3+ cells and total number of cells on the membrane in each treatment were counted (n, number of explants in each treatment); and percentage of PH3+ cells was calculated and tabulated as shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172437&req=5

fig6: Shh restricts the migration of NCCs. Migratory cells on the filter from explants cultured for 3 d in the presence of GDNF (A–C) or GDNF + Shh (D–F) were stained for TUJ1 (A and D, green), Ret (B and E, red), or PH3 (C and F, red). PH3+ cells and total number of cells on the membrane in each treatment were counted (n, number of explants in each treatment); and percentage of PH3+ cells was calculated and tabulated as shown.
Mentions: The migratory cells that were collected from the membrane for counting expressed Ret and TUJ1, confirming that these cells were derivatives of enteric NCCs (Fig. 5 N). Few NCCs migrated out of the explants in the absence of GDNF. Addition of Shh reduced the number of migratory NCCs by half, as compared with those treated with GDNF alone (Fig. 5 N; P = 0.003; t test). NCCs on the membrane had differentiated into neurons as they expressed TUJ1 (Fig. 6, A and D). However, some of these TUJ1+ cells were still proliferating as revealed by PH3 immunoreactivity (Fig. 6, A–F). The proportion of PH3+ cells on the membrane was similar between the cultures with or without Shh, indicating that the proliferation of cells on the membrane was comparable in these cultures (P > 0.05; t test). This finding suggested that the variable numbers of cells on the membrane in various treatments was not the consequence of different proliferation of migratory cells on the membrane. In other words, the numbers of cells on the membrane could reflect the number of migratory NCCs from the explants in response to different factors.

Bottom Line: 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.Our data suggest that Shh controls the proliferation and differentiation of NCCs and modulates the responsiveness of NCCs toward GDNF inductions.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The University of Hong Kong, 21 Sassoon Rd., Pokfulam, Hong Kong, HKSAR China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus