Foxd1 is required for terminal differentiation of anterior hypothalamic neuronal subtypes

Although the hypothalamus functions as a master homeostat for many behaviors, little is known about the transcriptional networks that control its development. To investigate this question, we analyzed mice deficient for the Forkhead domain transcription factor Foxd1. Foxd1 is selectively expressed in neuroepithelial cells of the prethalamus and hypothalamus prior to the onset of neurogenesis, and is later restricted to neural progenitors of the prethalamus and anterior hypothalamus. During early stages of neurogenesis, we observed that Foxd1-deficient mice showed reduced expression of Six3 and Vax1 in anterior hypothalamus, but overall patterning of the prethalamus and hypothalamus is unaffected. After neurogenesis is complete, however, a progressive reduction and eventual loss of expression of molecular markers of the suprachiasmatic, paraventricular and periventricular hypothalamic is observed. These findings demonstrate that Foxd1 acts in hypothalamic progenitors to allow sustained expression of a subset of genes selectively expressed in mature neurons of the anterior hypothalamus. We measured gene expression profiles of wild-type and Foxd1-mutant hypothalamic tissues separately at E12.0, E12.5 and E17.5尽管下丘脑（hypothalamus）是调控多种行为的核心稳态调节枢纽，但目前学界对调控其发育的转录调控网络仍知之甚少。为探究这一科学问题，本研究对叉头框结构域转录因子Foxd1功能缺陷型小鼠开展了分析。Foxd1在神经发生（neurogenesis）启动前，选择性表达于前丘脑（prethalamus）与下丘脑的神经上皮细胞中，后续则仅局限于前丘脑与下丘脑前部的神经前体细胞内。在神经发生早期阶段，我们观察到Foxd1缺陷型小鼠的下丘脑前部中，Six3与Vax1的表达水平显著降低，但前丘脑与下丘脑的整体模式构建未受影响。然而，在神经发生完成后，视交叉上、室旁及室周下丘脑核团的分子标记物表达呈现进行性下降，并最终完全丢失。上述研究结果表明，Foxd1可通过作用于下丘脑前体细胞，维持下丘脑前部成熟神经元中特异性表达的部分基因的持续表达。本研究分别在胚胎发育第12.0天（E12.0）、第12.5天（E12.5）及第17.5天（E17.5），对野生型与Foxd1突变型下丘脑组织的基因表达谱进行了检测。