Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells
Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells
复制标题
DOI：
10.1242/dev.01429
复制
发表时间：
2004-11-01
期刊：
影响因子：
4.6
通讯作者：
Morrison, SJ
中科院分区：
文献类型：
--
作者：
Joseph, NM;Mukouyama, YS;Morrison, SJ
神经嵴干细胞（NCSC）在整个妊娠晚期持续存在于外周神经中，但其功能尚不清楚。目前的神经发育模型只考虑神经嵴的Schwarnn细胞的产生，但NCSCs的存在提高了多系分化的可能性。我们进行了Crerecombinase命运映射以确定哪些神经细胞是神经嵴衍生的。神经内膜成纤维细胞，除了髓鞘和非髓鞘Schwarnn细胞，神经嵴衍生，而神经束膜细胞，周细胞和内皮细胞没有。这将神经内膜成纤维细胞鉴定为一种新的神经嵴衍生物，并证明了躯干神经嵴在体内确实产生成纤维细胞，这与先前对培养的躯干NCSC的研究一致。在发育中的神经中，NCSC向神经胶质和非神经胶质衍生物的多谱系分化似乎受到神经调节蛋白、notch配体和骨形态发生蛋白的调节，因为这些因子在发育中的神经中表达，并导致神经NCSC在培养中产生雪旺细胞和成纤维细胞，而不是神经元。因此，神经发育比以前认为的更复杂，涉及NCSC自我更新，谱系承诺和多谱系分化。
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 Schwarnn cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Crerecombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwarnn 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.