Chun J J, Shatz C J
Department of Neurobiology, Stanford University School of Medicine, California 94305.
J Neurosci. 1989 May;9(5):1648-67. doi: 10.1523/JNEUROSCI.09-05-01648.1989.
The earliest-generated neurons of the cat cerebral cortex have been studied here during development using a combination of 3H-thymidine birthdating with immunohistochemistry for the neuron-specific protein MAP2 or for several neuropeptides/transmitters. These neurons are the first postmitotic cells of the cortex, with birthdates during the 1-week period preceding the genesis of cells of the adult cerebral cortex (Luskin and Shatz, 1985a; Chun et al., 1987). However, they are transient and the majority disappear by adulthood (Luskin and Shatz, 1985a; Chun and Shatz, 1989). When autoradiographic birthdating is combined with MAP2 immunostaining during fetal life, the entire population of these early-generated neurons appears to be stained, resulting in labeled bands above and below the cortical plate. The band above the cortical plate (in the marginal zone) contains early-generated neurons with horizontal morphologies, while the thicker band beneath the cortical plate (within the intermediate zone) contains the somata of early-generated neurons and their elaborate processes that are frequently directed towards the ventricular surface. In view of the correspondence between the location of the early-generated neurons and the MAP2-immunostained band beneath the cortical plate, we suggest that this combined approach can be used to define accurately the subdivision of the intermediate zone known as the subplate. The early-generated neurons are also immunoreactive for GABA, neuropeptide Y (NPY), somatostatin (SRIF), and cholecystokinin (CCK) during fetal life. While GABA, NPY, and SRIF immunostaining could be detected by embryonic day 50 (E50), that for CCK was not found until E60. Moreover, there is a relationship between neuropeptide immunoreactivity and location within the cerebral wall. The marginal-zone neurons are immunoreactive only for CCK. The subplate neurons are immunoreactive for CCK, SRIF, and NPY. Most of those immunoreactive for SRIF tend to be clustered within the upper part of the subplate, while those immunoreactive for NPY tend to be located more deeply. Cells immunoreactive for GABA are more uniformly distributed throughout the cerebral wall. These observations demonstrate directly that the marginal zone and subplate contain peptide- and GABA-immunoreactive neurons that belong to the earliest-generated cell population of the cerebral cortex. The presence of these early-generated neurons, which achieve a remarkable degree of maturity during fetal life, suggests that they perform an essential, yet transient, role in the development of the cerebral cortex.
本文利用³H-胸腺嘧啶核苷出生时间标记法与针对神经元特异性蛋白MAP2或几种神经肽/神经递质的免疫组织化学相结合的方法,对猫大脑皮质发育过程中最早产生的神经元进行了研究。这些神经元是皮质的首批有丝分裂后细胞,其出生日期在成人大脑皮质细胞发生前的1周内(卢斯金和沙茨,1985a;春等人,1987)。然而,它们是短暂存在的,大多数在成年期消失(卢斯金和沙茨,1985a;春和沙茨,1989)。在胎儿期,当放射自显影出生时间标记法与MAP2免疫染色相结合时,这些早期产生的神经元似乎全部被染色,在皮质板上方和下方形成标记带。皮质板上方的带(在边缘区)包含具有水平形态的早期产生的神经元,而皮质板下方较厚的带(在中间区内)包含早期产生的神经元的胞体及其通常指向脑室表面的精细突起。鉴于早期产生的神经元的位置与皮质板下方MAP2免疫染色带之间的对应关系,我们认为这种联合方法可用于准确界定中间区中称为板下带的细分区域。在胎儿期,早期产生的神经元对γ-氨基丁酸(GABA)、神经肽Y(NPY)、生长抑素(SRIF)和胆囊收缩素(CCK)也具有免疫反应性。虽然在胚胎第50天(E50)就能检测到GABA、NPY和SRIF免疫染色,但直到E60才发现CCK的免疫染色。此外,神经肽免疫反应性与脑壁内的位置之间存在关联。边缘区神经元仅对CCK具有免疫反应性。板下带神经元对CCK、SRIF和NPY具有免疫反应性。大多数对SRIF具有免疫反应性的神经元倾向于聚集在板下带的上部,而对NPY具有免疫反应性的神经元倾向于位于更深的位置。对GABA具有免疫反应性的细胞在整个脑壁中分布更为均匀。这些观察结果直接表明,边缘区和板下带含有属于大脑皮质最早产生的细胞群体的肽和GABA免疫反应性神经元。这些在胎儿期就达到显著成熟程度的早期产生的神经元的存在,表明它们在大脑皮质发育中发挥着重要但短暂的作用。