Doughty M L, Delhaye-Bouchaud N, Mariani J
Laboratoire de Neurobiologie du Développement, Institut des Neurosciences (URA CNRS 1488), Université P. et M. Curie, Paris, France.
J Comp Neurol. 1998 Sep 28;399(3):306-20.
Cerebellar pattern formation was investigated in rats treated with DNA modifying agents. Animals were subjected to combinations of daily injections of methylazoxymethanol acetate (MAM) for the last 6 days gestation and/or localised X-irradiation of the hindbrain on postnatal days 1 and 5 (P1 and P5). Animals were analysed on embryonic day 18 (E18), P0, P3, P7, and P14. Five parameters of the cerebellum were recorded from midsagittal sections: the number of primary lobules; the thickness of the external germinal layer (EGL); the density of cells in the internal granule cell layer (IGL) region; and the midsagittal area and perimeter. In addition, the laterolateral cerebellar distance was calculated. The data demonstrate that pre- and postnatal reduction of the EGL results in reduced cerebellar growth and folding. Cessation of the treatment at birth results in a recovery and eventual overproduction of EGL, but cerebellar growth and the development of fissures lags behind that of normal rats. Pre- and postnatal destruction of the EGL severely limited cerebellar growth and fissuration, and the cerebella contained only five primary lobules at P14. Rats subjected to postnatal X-irradiation alone had a similar low density of granule cells relative to those treated with a combination of prenatal MAM injections and postnatal X-irradiation, and yet the cerebella contained deeper fissures and more lobules (nine at P14). The data indicate that there are two phases of cerebellar folding: the establishment of five lobules that arise independent of granule cell production, and the granule cell-dependent expansion and partitioning of these five principal lobules during postnatal development. We propose that the lack of correlation between the severity of the granule cell loss and degree of lobulation in agranular rats indicates that granule cells exert an inductive influence over lobulation that is in part independent of the forces generated by their production and differentiation.
在接受DNA修饰剂处理的大鼠中研究了小脑模式形成。在妊娠的最后6天，动物每天接受乙酸甲基偶氮甲醇（MAM）注射，和/或在出生后第1天和第5天（P1和P5）对后脑进行局部X射线照射。在胚胎第18天（E18）、P0、P3、P7和P14对动物进行分析。从矢状面切片记录小脑的五个参数：初级小叶的数量；外颗粒层（EGL）的厚度；内颗粒细胞层（IGL）区域的细胞密度；以及矢状面面积和周长。此外，计算小脑的左右距离。数据表明，产前和产后EGL减少会导致小脑生长和折叠减少。出生时停止治疗会导致EGL恢复并最终过度生成，但小脑生长和裂沟发育落后于正常大鼠。产前和产后EGL破坏严重限制了小脑生长和裂沟形成，在P14时小脑仅包含五个初级小叶。单独接受产后X射线照射的大鼠相对于接受产前MAM注射和产后X射线照射联合处理的大鼠，颗粒细胞密度同样较低，然而小脑裂沟更深且小叶更多（P14时为九个）。数据表明小脑折叠有两个阶段：五个小叶的形成独立于颗粒细胞产生，以及在出生后发育过程中这五个主要小叶依赖颗粒细胞的扩展和划分。我们提出，颗粒细胞缺失的严重程度与无颗粒大鼠小叶化程度之间缺乏相关性，表明颗粒细胞对小叶化施加诱导影响，这种影响部分独立于其产生和分化所产生的力量。
