Lavdas A A, Mione M C, Parnavelas J G
Department of Anatomy and Developmental Biology, University College, London WC1E 6BT, UK.
Cereb Cortex. 1996 May-Jun;6(3):490-7. doi: 10.1093/cercor/6.3.490.
The mammalian cerebral cortex, although a structure of great complexity, is characterized by a high degree of organization where the proportions, spatial relationships, and properties of the various cell types are rigidly controlled. The mechanisms responsible for the creation of such a rigid distribution of cell types are not known. Lineage studies in adult rats have suggested that each of the cortical progenitor cells lining the telencephalic ventricles during embryonic development gives rise to progeny of the same phenotype (homogeneous clones). However, the possibility that homogeneous clones are the result of complex processes affecting both the final number and the phenotype of clonally related cells during development has not been investigated. In the present study, we followed the development of cortical cell lineages labeled with retroviral injections at embryonic day (E) 16 in rats of 7, 14, or 21 d of age using electron microscopy and immunocytochemistry for the neurotransmitters glutamate and GABA. We found that a significant number of cortical clones at postnatal day (P) 7 and P14, and fewer at P21, showed mixed pyramidal/nonpyramidal cell composition. We sometimes observed that "mixed" neuronal clones contained cells immunoreactive for both glutamate and GABA. In the general population of cortical cells, "bireactive" neurons represented 3.7% of all neurons at P7, 18% at P14, and 0.6% in adult rats. Although the change in the composition of neuronal clones between the third week of postnatal life and adulthood may be due to changes in the phenotype of some developing neurons, we would like to suggest that it is probably due to selective neuronal cell death.
哺乳动物的大脑皮层虽然结构极为复杂，但其特点是具有高度的组织性，其中各种细胞类型的比例、空间关系和特性都受到严格控制。造成这种细胞类型严格分布的机制尚不清楚。对成年大鼠的谱系研究表明，胚胎发育期间沿端脑脑室排列的每个皮质祖细胞都会产生相同表型的后代（同质克隆）。然而，同质克隆是发育过程中影响克隆相关细胞的最终数量和表型的复杂过程的结果这一可能性尚未得到研究。在本研究中，我们利用电子显微镜和针对神经递质谷氨酸和γ-氨基丁酸的免疫细胞化学方法，追踪了在胚胎第16天（E16）经逆转录病毒注射标记的大鼠在7、14或21日龄时皮质细胞谱系的发育情况。我们发现，在出生后第7天（P7）和P14时有相当数量的皮质克隆呈现混合的锥体/非锥体细胞组成，而在P21时则较少。我们有时观察到“混合”神经元克隆包含对谷氨酸和γ-氨基丁酸均有免疫反应性的细胞。在皮质细胞的总体中，“双反应性”神经元在P7时占所有神经元的3.7%，在P14时占18%，在成年大鼠中占0.6%。虽然出生后第三周与成年期之间神经元克隆组成的变化可能是由于一些发育中神经元表型的改变，但我们认为这可能是由于选择性神经元细胞死亡所致。
