Cipriani Sara, Journiac Nathalie, Nardelli Jeannette, Verney Catherine, Delezoide Anne-Lise, Guimiot Fabien, Gressens Pierre, Adle-Biassette Homa
INSERM UMR 1141, Hôpital Robert-Debré, Paris, France.
Faculté de Médecine Denis Diderot, Université Paris 7, Paris, France.
Cereb Cortex. 2017 Jan 1;27(1):358-372. doi: 10.1093/cercor/bhv223.
The molecular mechanisms that orchestrate the development of the human dentate gyrus are not known. In this study, we characterized the formation of human dentate and fimbrial progenitors and postmitotic neurons from 9 gestational weeks (GW9) to GW25. PAX6+ progenitor cells remained proliferative until GW16 in the dentate ventricular zone. By GW11, the secondary dentate matrix had developed in the intermediate zone, surrounding the dentate anlage and streaming toward the subpial layer. This secondary matrix contained proliferating PAX6+ and/or TBR2+ progenitors. In parallel, SOX2+ and PAX6+ fimbrial cells were detected approaching the dentate anlage, representing a possible source of extra-dentate progenitors. By GW16, when the granule cell layer could be delineated, a hilar matrix containing PAX6+ and some TBR2+ progenitors had become identifiable. By GW25, when the 2 limbs of the granule cell layer had formed, the secondary dentate matrix was reduced to a pool of progenitors at the fimbrio-dentate junction. Although human dentate development recapitulates key steps previously described in rodents, differences seemed to emerge in neuron layer markers expression. Further studies are necessary to better elucidate their role in dentate formation and connectivity.
协调人类齿状回发育的分子机制尚不清楚。在本研究中，我们对9个孕周（GW9）至GW25的人类齿状和伞部祖细胞以及有丝分裂后神经元的形成进行了特征描述。在齿状脑室区，PAX6+祖细胞在GW16之前一直保持增殖状态。到GW11时，中间区已发育出次级齿状基质，围绕着齿状原基并流向软膜下层。这种次级基质含有增殖的PAX6+和/或TBR2+祖细胞。同时，检测到SOX2+和PAX6+伞部细胞接近齿状原基，这代表了齿状外祖细胞的一个可能来源。到GW16时，当颗粒细胞层可以被勾勒出来时，含有PAX6+和一些TBR2+祖细胞的海马基质变得可识别。到GW25时，当颗粒细胞层的两个分支形成时，次级齿状基质减少为齿状-伞部交界处的祖细胞池。尽管人类齿状回发育概括了先前在啮齿动物中描述的关键步骤，但在神经元层标记物表达方面似乎出现了差异。需要进一步研究以更好地阐明它们在齿状回形成和连接中的作用。
