Abstract
Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neural crest derived, whereas perineurial cells, pericytes and endothelial cells were not. This identified endoneurial fibroblasts as a novel neural crest derivative, and demonstrated that trunk neural crest does give rise to fibroblasts in vivo, consistent with previous studies of trunk NCSCs in culture. The multilineage differentiation of NCSCs into glial and non-glial derivatives in the developing nerve appears to be regulated by neuregulin, notch ligands, and bone morphogenic proteins, as these factors are expressed in the developing nerve, and cause nerve NCSCs to generate Schwann cells and fibroblasts, but not neurons, in culture. Nerve development is thus more complex than was previously thought, involving NCSC self-renewal, lineage commitment and multilineage differentiation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5599-5612 |
| Number of pages | 14 |
| Journal | Development |
| Volume | 131 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 2004 |
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Keywords
- Fate-mapping
- Neural crest stem cell
- Peripheral nerve development
ASJC Scopus subject areas
- Anatomy
- Cell Biology
Cite this
Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. / Joseph, Nancy M.; Mukouyama, Yoh Suke; Mosher, Jack T.; Jaegle, Martine; Crone, Steven A.; Dormand, Emma Louise; Lee, Kuo Fen; Meijer, Dies; Anderson, David J.; Morrison, Sean J.
In: Development, Vol. 131, No. 22, 11.2004, p. 5599-5612.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells
AU - Joseph, Nancy M.
AU - Mukouyama, Yoh Suke
AU - Mosher, Jack T.
AU - Jaegle, Martine
AU - Crone, Steven A.
AU - Dormand, Emma Louise
AU - Lee, Kuo Fen
AU - Meijer, Dies
AU - Anderson, David J.
AU - Morrison, Sean J.
PY - 2004/11
Y1 - 2004/11
N2 - Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neural crest derived, whereas perineurial cells, pericytes and endothelial cells were not. This identified endoneurial fibroblasts as a novel neural crest derivative, and demonstrated that trunk neural crest does give rise to fibroblasts in vivo, consistent with previous studies of trunk NCSCs in culture. The multilineage differentiation of NCSCs into glial and non-glial derivatives in the developing nerve appears to be regulated by neuregulin, notch ligands, and bone morphogenic proteins, as these factors are expressed in the developing nerve, and cause nerve NCSCs to generate Schwann cells and fibroblasts, but not neurons, in culture. Nerve development is thus more complex than was previously thought, involving NCSC self-renewal, lineage commitment and multilineage differentiation.
AB - Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neural crest derived, whereas perineurial cells, pericytes and endothelial cells were not. This identified endoneurial fibroblasts as a novel neural crest derivative, and demonstrated that trunk neural crest does give rise to fibroblasts in vivo, consistent with previous studies of trunk NCSCs in culture. The multilineage differentiation of NCSCs into glial and non-glial derivatives in the developing nerve appears to be regulated by neuregulin, notch ligands, and bone morphogenic proteins, as these factors are expressed in the developing nerve, and cause nerve NCSCs to generate Schwann cells and fibroblasts, but not neurons, in culture. Nerve development is thus more complex than was previously thought, involving NCSC self-renewal, lineage commitment and multilineage differentiation.
KW - Fate-mapping
KW - Neural crest stem cell
KW - Peripheral nerve development
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U2 - 10.1242/dev.01429
DO - 10.1242/dev.01429
M3 - Article
VL - 131
SP - 5599
EP - 5612
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 22
ER -