Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
Cereb Cortex. 2014 May;24(5):1361-72. doi: 10.1093/cercor/bhs421. Epub 2013 Jan 10.
Early brain development is regulated by the coordinated actions of multiple signaling centers at key boundaries between compartments. Three telencephalic midline structures are in a position to play such roles in forebrain patterning: The cortical hem, the septum, and the thalamic eminence at the diencephalic-telencephalic boundary. These structures express unique complements of signaling molecules, and they also produce distinct populations of Cajal-Retzius cells, which are thought to act as "mobile patterning units," migrating tangentially to cover the telencephalic surface. We show that these 3 structures require the transcription factor Lhx2 to delimit their extent. In the absence of Lhx2 function, all 3 structures are greatly expanded, and the Cajal-Retzius cell population is dramatically increased. We propose that the hem, septum, and thalamic eminence together form a "forebrain hem system" that defines and regulates the formation of the telencephalic midline. Disruptions in the forebrain hem system may be implicated in severe brain malformations such as holoprosencephaly. Lhx2 functions as a central regulator of this system's development. Since all components of the forebrain hem system have been identified across several vertebrate species, the mechanisms that regulate them may have played a fundamental role in driving key aspects of forebrain evolution.
早期大脑发育受多个信号中心在隔室之间关键边界的协调作用调控。三个端脑中线结构处于在大脑前脑模式形成中发挥这种作用的位置：皮质核、隔核和神经-大脑交界处的丘脑隆起。这些结构表达独特的信号分子组合，并且它们还产生独特的 Cajal-Retzius 细胞群体，这些细胞被认为是作为“可移动的模式单元”，沿着切线迁移以覆盖大脑皮层表面。我们表明，这 3 个结构需要转录因子 Lhx2 来限定其范围。在没有 Lhx2 功能的情况下，所有 3 个结构都大大扩大，Cajal-Retzius 细胞群体显著增加。我们提出，皮质核、隔核和丘脑隆起共同形成一个“大脑前脑核系统”，该系统定义并调节大脑中线的形成。前脑核系统的破坏可能与严重的脑畸形如全前脑畸形有关。Lhx2 作为该系统发育的中央调节剂。由于前脑核系统的所有成分在几个脊椎动物物种中都已被识别，因此调节它们的机制可能在推动大脑前脑进化的关键方面发挥了重要作用。
