Department of Biology, San Diego State University, San Diego, CA, USA.
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Dev Cell. 2018 Nov 5;47(3):331-347.e5. doi: 10.1016/j.devcel.2018.10.014.
SoxB1 genes play fundamental roles in neurodevelopmental processes and maintaining stem cell multipotency, but little is known about their function in regeneration. We addressed this question by analyzing the activity of the SoxB1 homolog soxB1-2 in the planarian Schmidtea mediterranea. Expression and functional analysis revealed that soxB1-2 marks ectodermal-lineage progenitors, and its activity is required for differentiation of subsets of ciliated epidermal and neuronal cells. Moreover, we show that inhibiting soxB1-2 or its candidate target genes leads to abnormal sensory neuron regeneration that causes planarians to display seizure-like movements or phenotypes associated with the loss of sensory modalities. Our analyses highlight soxB1-2-regulated genes that are expressed in sensory neurons and are homologous to factors implicated in epileptic disorders in humans and animal models of epilepsy, indicating that planarians can serve as a complementary model to investigate genetic causes of epilepsy.
SoxB1 基因在神经发育过程和维持干细胞多能性方面发挥着重要作用，但它们在再生中的功能知之甚少。我们通过分析环节动物 Schmidtea mediterranea 中的 SoxB1 同源物 soxB1-2 的活性来解决这个问题。表达和功能分析表明，soxB1-2 标记外胚层谱系祖细胞，其活性对于纤毛表皮和神经元细胞亚群的分化是必需的。此外，我们还表明，抑制 soxB1-2 或其候选靶基因会导致异常的感觉神经元再生，从而导致涡虫表现出类似癫痫发作的运动或与感觉方式丧失相关的表型。我们的分析强调了 soxB1-2 调控的基因，这些基因在感觉神经元中表达，与人类癫痫症和癫痫动物模型中涉及的因子同源，表明涡虫可以作为一种补充模型，用于研究癫痫症的遗传原因。
