Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Karlsruhe, Germany.
PLoS Biol. 2011 Dec;9(12):e1001218. doi: 10.1371/journal.pbio.1001218. Epub 2011 Dec 13.
Initial axial patterning of the neural tube into forebrain, midbrain, and hindbrain primordia occurs during gastrulation. After this patterning phase, further diversification within the brain is thought to proceed largely independently in the different primordia. However, mechanisms that maintain the demarcation of brain subdivisions at later stages are poorly understood. In the alar plate of the caudal forebrain there are two principal units, the thalamus and the pretectum, each of which is a developmental compartment. Here we show that proper neuronal differentiation of the thalamus requires Lhx2 and Lhx9 function. In Lhx2/Lhx9-deficient zebrafish embryos the differentiation process is blocked and the dorsally adjacent Wnt positive epithalamus expands into the thalamus. This leads to an upregulation of Wnt signaling in the caudal forebrain. Lack of Lhx2/Lhx9 function as well as increased Wnt signaling alter the expression of the thalamus specific cell adhesion factor pcdh10b and lead subsequently to a striking anterior-posterior disorganization of the caudal forebrain. We therefore suggest that after initial neural tube patterning, neurogenesis within a brain compartment influences the integrity of the neuronal progenitor pool and border formation of a neuromeric compartment.
神经管的初始轴向模式形成，将脑分为前脑、中脑和后脑原基，发生在原肠胚形成期。在这个模式形成阶段之后，人们认为大脑内部的进一步多样化主要在不同的原基中独立进行。然而，维持大脑细分边界的机制在后期阶段还了解甚少。在尾侧前脑的翼板中有两个主要的单位，丘脑和顶盖，每个都是一个发育的隔室。在这里，我们发现 Lhx2 和 Lhx9 的功能对于丘脑的正常神经元分化是必需的。在 Lhx2/Lhx9 缺陷的斑马鱼胚胎中，分化过程被阻断，并且与背侧相邻的 Wnt 阳性上丘脑扩展到丘脑。这导致尾侧前脑的 Wnt 信号通路的上调。Lhx2/Lhx9 功能的缺失以及 Wnt 信号通路的增加改变了丘脑特异性细胞粘附因子 pcdh10b 的表达，随后导致尾侧前脑的显著前后组织紊乱。因此，我们认为，在初始神经管模式形成之后，脑隔室内的神经发生会影响神经元祖细胞池的完整性和神经节段隔室的边界形成。
