Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of histology and embryology, School of Medicine, Southeast University, Nanjing 210009, China.
Tongji Hospital, Brain and Spinal Cord Innovative Research Center, School of Life Sciences and Technology, Tongji University, Shanghai 200065, China.
Cereb Cortex. 2019 Dec 17;29(12):4968-4981. doi: 10.1093/cercor/bhz037.
During early development, signaling centers, such as the cortical hem and the preoptic area (POA), are critical for telencephalic patterning. However, the mechanisms underlying the maintenance of signal centers are poorly understood. Here, we report that the transcription factor Foxg1 is required to confine the POA, a resource of Sonic Hedgehog (Shh) that is pivotal for ventral telencephalic development. Cell-specific deletion of Foxg1 achieved by crossing Foxg1fl/fl with Dbx1-cre or Nestin-CreER combined with tamoxifen induction results in a dramatic expansion of the POA accompanied by the significantly increased activity of the Shh signaling pathway. Ventral pattern formation was severely impaired. Moreover, we demonstrated that Foxg1 directly represses Dbx1 to restrict the POA. Furthermore, we found that the ventral pallium was expanded, which might also contribute to the observed patterning defects. These findings will improve our understanding of the maintenance of signal centers and help to elucidate the mechanisms underlying ventral telencephalic patterning.
在早期发育过程中，皮质半球和视前区（POA）等信号中心对于端脑的模式形成至关重要。然而，维持信号中心的机制还知之甚少。在这里，我们报告转录因子 Foxg1 对于限制 POA 是必需的，POA 是 Sonic Hedgehog（Shh）的一个资源，对于腹侧端脑的发育至关重要。通过 Foxg1fl/fl 与 Dbx1-cre 或 Nestin-CreER 交叉并结合他莫昔芬诱导实现的 Foxg1 的细胞特异性缺失导致 POA 的显著扩张，伴随着 Shh 信号通路的显著激活。腹侧模式形成受到严重损害。此外，我们证明 Foxg1 直接抑制 Dbx1 以限制 POA。此外，我们发现腹侧苍白球扩张，这也可能导致观察到的模式缺陷。这些发现将提高我们对信号中心维持的理解，并有助于阐明腹侧端脑模式形成的机制。
