Temporal control of Wnt signaling is required for habenular neuron diversity and brain asymmetry
Temporal control of Wnt signaling is required for habenular neuron diversity and brain asymmetry
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DOI：
10.1242/dev.182865
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发表时间：
2020-03-01
期刊：
影响因子：
4.6
通讯作者：
Carl, Matthias
中科院分区：
文献类型：
--
作者：
Guglielmi, Luca;Buehler, Anja;Carl, Matthias
在胚胎发育过程中，信号过程的精确时间协调是细胞分化的关键。大量的分泌分子由细胞和组织产生和释放，并在细胞外空间移动。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控机制网络，而这些机制往往没有被很好地理解。斑马鱼保守的左右两侧非对称形成的缰核是研究信号控制如何促进特定神经元种群产生的极好模型。WNT信号是缰核神经元类型、不对称性和轴突连通性所必需的。然而，这一途径的时间调节以及参与其中的参与者仍不清楚。我们发现，缰核前体细胞中Wnt信号活性受到严格调控的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，通过该机制，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。这一机制可能适用于其他类型的细胞，包括肿瘤细胞。
Precise temporal coordination of signaling processes is pivotal for cellular differentiation duringembryonic development. Avast 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, 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.