Heidelberg University, Medical Faculty Mannheim, Department of Cell and Molecular Biology, 68167 Mannheim, Germany.
University of Trento, Department of Cellular, Computational and Integrative Biology (CIBIO), 38123 Trento, Italy.
Development. 2020 Mar 16;147(6):dev182865. doi: 10.1242/dev.182865.
Precise temporal coordination of signaling processes is pivotal for cellular differentiation during embryonic development. A vast number of secreted molecules are produced and released by cells and tissues, and travel in the extracellular space. Whether they induce a signaling pathway and instruct cell fate, however, depends on a complex network of regulatory mechanisms, which are often not well understood. The conserved bilateral left-right asymmetrically formed habenulae of the zebrafish are an excellent model for investigating how signaling control facilitates the generation of defined neuronal populations. Wnt signaling is required for habenular neuron type specification, asymmetry and axonal connectivity. The temporal regulation of this pathway and the players involved have, however, have remained unclear. We find that tightly regulated temporal restriction of Wnt signaling activity in habenular precursor cells is crucial for the diversity and asymmetry of habenular neuron populations. We suggest a feedback mechanism whereby the tumor suppressor Wnt inhibitory factor Wif1 controls the Wnt dynamics in the environment of habenular precursor cells. This mechanism might be common to other cell types, including tumor cells.
在胚胎发育过程中，信号过程的精确时间协调对细胞分化至关重要。大量的分泌分子由细胞和组织产生并释放，并在细胞外空间中移动。然而，它们是否诱导信号通路并指示细胞命运，取决于一个复杂的调节机制网络，而这些机制往往并不清楚。斑马鱼两侧对称形成的缰核是研究信号控制如何促进特定神经元群体产生的理想模型。Wnt 信号对于缰核神经元类型的特化、不对称和轴突连接至关重要。然而，该途径的时间调控及其涉及的参与者仍不清楚。我们发现，缰核前体细胞中 Wnt 信号活性的严格时间限制对于缰核神经元群体的多样性和不对称性至关重要。我们提出了一种反馈机制，即肿瘤抑制因子 Wnt 抑制因子 Wif1 控制缰核前体细胞环境中的 Wnt 动力学。这种机制可能在包括肿瘤细胞在内的其他细胞类型中很常见。
