Tate Matthew C, Lindquist Robert A, Nguyen Thuhien, Sanai Nader, Barkovich A James, Huang Eric J, Rowitch David H, Alvarez-Buylla Arturo
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California - San Francisco, San Francisco, CA, 94143; Department of Neurological Surgery, University of California - San Francisco, San Francisco, CA, 94143.
J Comp Neurol. 2015 Feb 15;523(3):449-62. doi: 10.1002/cne.23690. Epub 2014 Dec 2.
Despite its critical importance to global brain function, the postnatal development of the human pons remains poorly understood. In the present study, we first performed magnetic resonance imaging (MRI)-based morphometric analyses of the postnatal human pons (0-18 years; n = 6-14/timepoint). Pons volume increased 6-fold from birth to 5 years, followed by continued slower growth throughout childhood. The observed growth was primarily due to expansion of the basis pontis. T2-based MRI analysis suggests that this growth is linked to increased myelination, and histological analysis of myelin basic protein in human postmortem specimens confirmed a dramatic increase in myelination during infancy. Analysis of cellular proliferation revealed many Ki67(+) cells during the first 7 months of life, particularly during the first month, where proliferation was increased in the basis relative to tegmentum. The majority of proliferative cells in the postnatal pons expressed the transcription factor Olig2, suggesting an oligodendrocyte lineage. The proportion of proliferating cells that were Olig2(+) was similar through the first 7 months of life and between basis and tegmentum. The number of Ki67(+) cells declined dramatically from birth to 7 months and further decreased by 3 years, with a small number of Ki67(+) cells observed throughout childhood. In addition, two populations of vimentin/nestin-expressing cells were identified: a dorsal group near the ventricular surface, which persists throughout childhood, and a parenchymal population that diminishes by 7 months and was not evident later in childhood. Together, our data reveal remarkable postnatal growth in the ventral pons, particularly during infancy when cells are most proliferative and myelination increases.
尽管脑桥对全球脑功能至关重要,但其出生后的发育情况仍知之甚少。在本研究中,我们首先对出生后的人类脑桥(0至18岁;每个时间点n = 6至14)进行了基于磁共振成像(MRI)的形态学分析。脑桥体积从出生到5岁增加了6倍,随后在整个儿童期持续缓慢增长。观察到的生长主要是由于脑桥基底部的扩张。基于T2的MRI分析表明,这种生长与髓鞘形成增加有关,对人类尸检标本中髓鞘碱性蛋白的组织学分析证实,婴儿期髓鞘形成显著增加。细胞增殖分析显示,在生命的前7个月,尤其是第一个月,有许多Ki67(+)细胞,其中脑桥基底部的增殖相对于被盖部有所增加。出生后脑桥中大多数增殖细胞表达转录因子Olig2,表明其为少突胶质细胞谱系。在生命的前7个月以及脑桥基底部和被盖部之间,Olig2(+)增殖细胞的比例相似。Ki67(+)细胞数量从出生到7个月急剧下降,并在3岁时进一步减少,在整个儿童期仅观察到少量Ki67(+)细胞。此外,还鉴定出了两组表达波形蛋白/巢蛋白的细胞:一组靠近脑室表面的背侧群体,在整个儿童期持续存在;另一组实质群体在7个月时减少,在儿童期后期不再明显。总之,我们的数据揭示了脑桥腹侧在出生后显著生长,尤其是在细胞增殖最活跃且髓鞘形成增加的婴儿期。