Young Heather M, Bergner Annette J, Müller Thomas
Department of Anatomy and Cell Biology, University of Melbourne, 3010, Victoria, Australia.
J Comp Neurol. 2003 Jan 27;456(1):1-11. doi: 10.1002/cne.10448.
Enteric neurons and glia arise from the neural crest. The phenotype of crest-derived cells was examined as they differentiated into neurons or glia in the mouse small and large intestine. Previous studies have shown that undifferentiated enteric crest-derived cells are Phox2b(+)/Ret(+)/p75(+)/Sox10(+), and at embryonic day (E) 10.5, about 10-15% of the crest-derived cells in the small intestine have started to differentiate into neurons. In the current study, by E12.5 and E14.5, about 25% and 47%, respectively, of Phox2b(+) cells in the small intestine were immunoreactive to the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did not change dramatically from E14.5 onward. The differentiation of crest-derived cells into neurons in the colon lagged behind that in the small intestine by several days. Differentiating enteric neurons showed high Ret, low p75, and undetectable Sox10 immunostaining. Glial precursors were identified by the presence of brain-specific fatty acid binding protein (B-FABP) and detected first in the fore- and rostral midgut at E11.5. Glial precursors appeared to be B-FABP(+)/Sox10(+)/p75(+) but showed low Ret immunostaining. S100b was not detected until E14.5. Adult glial cells were B-FABP(+)/Sox10(+)/p75(+)/S100b(+). A nucleic acid stain (to identify all ganglion cells) was combined with immunostaining for PGP9.5 and S100b to detect neurons and glial cells, respectively, in the postnatal intestine. At postnatal day 0, fewer than 5% and 10% of cells in myenteric ganglia of the small and large intestine, respectively, were neither PGP9.5(+) nor S100b(+). Because some classes of neurons are not present in significant numbers until after birth, the expression of PGP9.5 by developing enteric neurons appeared to precede the expression of neuron type-specific markers.
肠神经元和神经胶质细胞起源于神经嵴。在小鼠小肠和大肠中，当神经嵴来源的细胞分化为神经元或神经胶质细胞时，对其表型进行了检测。先前的研究表明，未分化的肠神经嵴来源细胞为Phox2b(+)/Ret(+)/p75(+)/Sox10(+)，在胚胎第（E）10.5天，小肠中约10-15%的神经嵴来源细胞开始分化为神经元。在本研究中，到E12.5和E14.5时，小肠中分别约25%和47%的Phox2b(+)细胞对泛神经元蛋白泛素水解酶（PGP9.5）呈免疫反应，且从E14.5往后该百分比没有显著变化。神经嵴来源的细胞在结肠中向神经元的分化比在小肠中落后几天。正在分化的肠神经元显示Ret高表达、p75低表达，且未检测到Sox10免疫染色。神经胶质前体细胞通过脑特异性脂肪酸结合蛋白（B-FABP）的存在得以鉴定，最早在E11.5时在前肠和吻侧中肠被检测到。神经胶质前体细胞似乎为B-FABP(+)/Sox10(+)/p75(+)，但Ret免疫染色较低。直到E14.5才检测到S100b。成年神经胶质细胞为B-FABP(+)/Sox10(+)/p75(+)/S100b(+)。一种核酸染色（用于识别所有神经节细胞）与PGP9.5和S100b的免疫染色相结合，分别用于检测出生后肠道中的神经元和神经胶质细胞。在出生后第0天，小肠和大肠肌间神经节中分别少于5%和10%的细胞既不是PGP9.5(+)也不是S100b(+)。由于某些类型的神经元直到出生后才大量存在，发育中的肠神经元中PGP9.5的表达似乎先于神经元类型特异性标志物的表达。
