Bokulić Ema, Medenica Tila, Bobić-Rasonja Mihaela, Milković-Periša Marija, Jovanov-Milošević Nataša, Judaš Miloš, Sedmak Goran
Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
Scientific Centre of Excellence for Basic, Clinical, and Translational Neuroscience, School of Medicine, University of Zagreb, Zagreb, Croatia.
Brain Struct Funct. 2025 Jan 20;230(2):33. doi: 10.1007/s00429-025-02893-w.
In this study, we analyzed the spatio-temporal pattern of expression of specific transcription factors (PITX2, FOXA1, BARHL1, FOXP1, FOXP2) in the human fetal subthalamic nucleus and its neighboring structures from 11 postconceptional weeks (PCW) to 3 postnatal months. We found that all analyzed transcription factors are expressed already during the early fetal period (at 11 PCW). Both FOXP1- and FOXP2-immunoreactive cells were found in the subthalamic nucleus as well as in the striatum, thalamus, reticular nucleus, but not in the zona incerta. FOXP2-ir cells were also found in the lateral hypothalamic-supramamillary area (LHA-SMA) and internal pallidal segment.On the other hand, PITX2, FOXA1 and BARHL1 were expressed exclusively in the subthalamic nucleus and LHA-SMA, from 11 PCW until the birth, the only exception being gradual loss of BARHL1 expression in the LHA-SMA during the late fetal period.Our findings present the first evidence in the human fetal brain that neurons of the subthalamic nucleus do not originate in the diencephalon, as was proposed by classical histological studies, but instead share a common hypothalamic (hp1 prosomere) origin with neurons of the LHA-SMA group, as proposed by the prosomeric model of brain development.
在本研究中，我们分析了从孕后11周（PCW）至出生后3个月期间，人类胎儿丘脑底核及其邻近结构中特定转录因子（PITX2、FOXA1、BARHL1、FOXP1、FOXP2）的时空表达模式。我们发现，所有分析的转录因子在胎儿早期（孕后11周）就已表达。在丘脑底核以及纹状体、丘脑、网状核中均发现了FOXP1和FOXP2免疫反应性细胞，但未定带中未发现。在外侧下丘脑-乳头体上区（LHA-SMA）和苍白球内侧段也发现了FOXP2免疫反应性细胞。另一方面，从孕后11周直至出生，PITX2、FOXA1和BARHL1仅在丘脑底核和LHA-SMA中表达，唯一的例外是在胎儿后期LHA-SMA中BARHL1表达逐渐丧失。我们的研究结果首次在人类胎儿大脑中证明，丘脑底核的神经元并非如经典组织学研究所提出的那样起源于间脑，而是如脑发育的前脑模型所提出的那样，与LHA-SMA组的神经元共享一个共同的下丘脑（前脑1原节）起源。
