Kopić Janja, Haldipur Parthiv, Millen Kathleen J, Kostović Ivica, Krasić Jure, Krsnik Željka
School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia.
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, USA.
Brain Struct Funct. 2024 Dec 18;230(1):13. doi: 10.1007/s00429-024-02865-6.
Early development of the human fetal cerebral cortex involves a set of precisely coordinated molecular processes that remains rather underexplored. Previous studies indicate that the laminar identity and the molecular specification of cortical neurons driven by genetic programming, as well as associated histogenetic events begin during early fetal development. Our recent study discovered unique regional cytoarchitectonic features in the developing human frontal lobe, including migratory waves of postmitotic neurons in the dorsal frontal cortex and the "double plate" feature in orbitobasal cortex (Kopić et al. in Cells 12:231, 2023). Notably, neurons of these two cytoarchitectonic features typically express deep projection neuron (DPN) markers (TBR1, TLE4, SOX5). This paper aims to conduct an in-depth investigation of these cytoarchitectonic features at the transcriptomic level, whilst preserving spatial information. Here, we employed NanoString GeoMx Digital Spatial Profiler (DSP) technology to examine gene expression differences in the transient cortical compartments of the dorsal and ventral regions of the developing frontal lobe, focusing specifically on 15 post-conceptional weeks (PCW), that is a critical period for subplate formation. We identified multiple differentially expressed genes between the transient cellular compartments of the dorsal and orbitobasal regions of the developing human frontal cortex. These new findings additionally confirm that regional patterning and specification of the prospective higher-order association prefrontal cortex emerges early in fetal development, contributing to the highly organized cortical architecture of the human brain.
人类胎儿大脑皮质的早期发育涉及一系列精确协调的分子过程，但仍未得到充分探索。先前的研究表明，由基因编程驱动的皮质神经元的层状身份和分子特化，以及相关的组织发生事件在胎儿早期发育期间就开始了。我们最近的研究发现了发育中的人类额叶独特的区域细胞结构特征，包括背侧额叶皮质中后有丝分裂神经元的迁移波和眶基底皮质中的“双板”特征（Kopić等人，《细胞》，2023年，第12卷，第231页）。值得注意的是，这两种细胞结构特征的神经元通常表达深部投射神经元（DPN）标记（TBR1、TLE4、SOX5）。本文旨在在转录组水平上对这些细胞结构特征进行深入研究，同时保留空间信息。在这里，我们采用了NanoString GeoMx数字空间分析（DSP）技术，以检查发育中的额叶背侧和腹侧区域的瞬时皮质区室中的基因表达差异，特别关注孕后15周（PCW），这是一个对亚板形成至关重要的时期。我们在发育中的人类额叶皮质的背侧和眶基底区域的瞬时细胞区室之间鉴定出多个差异表达基因。这些新发现进一步证实，未来高阶联合前额叶皮质的区域模式化和特化在胎儿发育早期就出现了，这有助于人类大脑高度有序的皮质结构。
