Skoff R P, Knapp P E
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Glia. 1991;4(2):165-74. doi: 10.1002/glia.440040208.
What precursor cells are the source of the macroglia generated during postnatal development? In order to answer this question, we studied the expression of glial specific antigens in proliferating neuroglia in postnatal rodent brain and optic nerve. Immunocytochemistry using antibodies to oligodendrocyte (OL) specific markers (sulfatide and galactocerebroside) and an astrocyte (AS) specific marker (glial fibrillary acidic protein) was combined with thymidine autoradiography. During the first week of postnatal development when most ASs are being generated, one third to one half of the proliferating cells in the optic system are positive for glial fibrillary acidic protein after a 1 h injection of thymidine (Skoff, Dev. Biol., 139:149-168, 1990). During the second postnatal week when OLs are being generated, 30 to 100% of the proliferating cells in presumptive white matter tracts are sulfatide positive and at least 10% are galactocerebroside positive. This finding demonstrates that ASs and OLs divide during postnatal development. These results confirm previous electron microscopic autoradiographic studies showing that the vast majority of proliferating cells in postnatal rat optic nerve have the morphologic characteristics of differentiating ASs or OLs (Skoff, J. Comp. Neurol., 169:291-312, 1976). Since proliferating ASs (astroblasts) and OLs (oligodendroblasts) constitute the majority of the dividing cells at the time that ASs and OLs are being generated, these glioblasts must be the major source for the macroglia generated postnatally. The findings strongly suggest that separate lineages exist for ASs and OLs during postnatal development. There is no compelling in vivo evidence for a bipotential progenitor cell that generates the majority of OLs and certain ASs in postnatal rodent brain. There may, of course, be distinct lineages for the subtypes of ASs and possibly even for subtypes of OLs. We review the concepts of commitment and plasticity and apply these terms to glial differentiation. In situ, the presence of oligodendroblasts and astroblasts demonstrates the COMMITMENT of proliferating cells to a specific glial lineage during normal development. Culture conditions may provide an environment that permits proliferating glial cells to vacillate in their selection of a specific lineage. This situation demonstrates developmental PLASTICITY and the ability of glia to adapt to an altered environment. Whether committed glial cells in situ can be induced to switch their lineage when normal CNS conditions are altered is an intriguing question that remains to be answered.
出生后发育过程中产生的大胶质细胞的前体细胞来源是什么？为了回答这个问题，我们研究了出生后啮齿动物脑和视神经中增殖神经胶质细胞中胶质细胞特异性抗原的表达。使用抗少突胶质细胞（OL）特异性标志物（硫脂和半乳糖脑苷脂）和星形胶质细胞（AS）特异性标志物（胶质纤维酸性蛋白）的抗体进行免疫细胞化学，并结合胸苷放射自显影术。在出生后发育的第一周，当大多数AS正在生成时，在注射胸苷1小时后，视系统中三分之一到一半的增殖细胞对胶质纤维酸性蛋白呈阳性（斯科夫，《发育生物学》，139:149 - 168，1990）。在出生后第二周，当OL正在生成时，假定白质束中30%至100%的增殖细胞硫脂呈阳性且至少10%半乳糖脑苷脂呈阳性。这一发现表明AS和OL在出生后发育过程中会分裂。这些结果证实了先前的电子显微镜放射自显影研究，该研究表明出生后大鼠视神经中绝大多数增殖细胞具有分化中的AS或OL的形态学特征（斯科夫，《比较神经学杂志》，169:291 - 312，1976）。由于增殖的AS（成星形细胞）和OL（成少突胶质细胞）在AS和OL生成时构成了分裂细胞的 majority，这些胶质母细胞必定是出生后产生的大胶质细胞的主要来源。这些发现强烈表明在出生后发育过程中AS和OL存在不同的谱系。在出生后啮齿动物脑中，没有令人信服的体内证据表明存在一种能产生大多数OL和某些AS的双能祖细胞。当然，AS的亚型甚至OL的亚型可能存在不同的谱系。我们回顾了定向分化和可塑性的概念，并将这些术语应用于胶质细胞分化。在原位，成少突胶质细胞和成星形细胞的存在表明在正常发育过程中增殖细胞向特定胶质谱系的定向分化。培养条件可能提供一种环境，使增殖的胶质细胞在选择特定谱系时产生波动。这种情况表明了发育可塑性以及胶质细胞适应改变环境的能力。当正常中枢神经系统条件改变时，原位的定向分化胶质细胞是否能被诱导改变其谱系是一个有待回答的有趣问题。
