Díaz-Hernández Martha Elena, Galván-Hernández Claudio Iván, Marín-Llera Jessica Cristina, Camargo-Sosa Karen, Bustamante Marcia, Wischin Sabina, Chimal-Monroy Jesús
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, Mexico.
Front Cell Dev Biol. 2021 Nov 8;9:703836. doi: 10.3389/fcell.2021.703836. eCollection 2021.
The spatiotemporal control of programmed cell death (PCD) plays a significant role in sculpting the limb. In the early avian limb bud, the anterior necrotic zone (ANZ) and the posterior necrotic zone are two cell death regions associated with digit number reduction. In this study, we evaluated the first events triggered by the FGF, BMP, and WNT signaling interactions to initiate cell death in the anterior margin of the limb to establish the ANZ. This study demonstrates that in a period of two to 8 h after the inhibition of WNT or FGF signaling or the activation of BMP signaling, cell death was induced in the anterior margin of the limb concomitantly with the regulation of , and expression. Comparing the gene expression profile between the ANZ and the undifferentiated zone at 22HH and 25HH and between the ANZ of 22HH and 25HH stages correlates with functional programs controlled by the regulatory network FGF, BMP, and WNT signaling in the anterior margin of the limb. This work provides novel insights to recognize a negative feedback loop between FGF8, BMP4, and DKK to control the onset of cell death in the anterior margin of the limb to the establishment of the ANZ.
程序性细胞死亡（PCD）的时空控制在塑造肢体过程中起着重要作用。在早期鸡胚肢体芽中，前坏死区（ANZ）和后坏死区是与指（趾）数减少相关的两个细胞死亡区域。在本研究中，我们评估了由FGF、BMP和WNT信号相互作用触发的最初事件，这些事件引发肢体前缘的细胞死亡以建立ANZ。本研究表明，在抑制WNT或FGF信号或激活BMP信号后的2至8小时内，肢体前缘诱导了细胞死亡，同时伴随着 、 和 表达的调节。比较22HH和25HH阶段ANZ与未分化区之间以及22HH和25HH阶段ANZ之间的基因表达谱，与肢体前缘由FGF、BMP和WNT信号调节网络控制的功能程序相关。这项工作为认识FGF8、BMP4和DKK之间的负反馈环提供了新的见解，该负反馈环控制肢体前缘细胞死亡的起始以建立ANZ。
