EFFECT OF BMP SIGNALS IN ANTERIOR AND POSTERIOR NEURAL MODELS ON REGULATING THE FGF PATHWAY

Xiliu Zhang^{1, #}, Mei Zhang^{1, #}, Zhongchuan Cheng², Peng Sun³, Yiqun Wang^{1, *}

¹Department of Neurology, The Fifth Hospital of WuHan, Wuhan, PR China - ²Department of Neurology, Traditional Chinese Medicine Hospital of Hong’an County, Huanggang, PR China - ³Department of Internal Medicine, Hubei University of Technology Hospital, Wuhan, PR China

Objective: To analyse the effect of the bone morphogenetic protein (BMP) signal on regulating the fibroblast growth factor (FGF) pathway in anterior and posterior neural models, and to investigate the specific mechanism of how FGF action is eliminated by the neural plate in the early development of vertebrates. 

Methods: The levels of the phosphorylated extracellular signal-associated kinase (p-ERK) in the dorsal ectoderm along the anterior-posterior (A-P) axis of the ganglion stage embryos were measured. FGF signalling activity was detected to determine the hierarchical activity model of the BMP and FGF signals. We also detected whether BMP could inhibit the FGF signal and analysed whether the signal was involved in the anterior nerve induction by controlling FGF signal transduction using SU5402. Also, we investigated whether BMP4 can inhibit the expression of FGF8-induced Flrt3. 

Results: The findings of this study indicated that BMP signals can act as an antagonist of FGF signalling in the A-P neural model in Xenopus laevis embryos. During the ganglion phase, BMP signals were up-regulated in the anterior nerve plate, showing a hierarchical model along the A-P axis. Inhibiting the late BMP signal transduction after the formation of intermediate gastrula embryos eliminated the expression of the anterior nerve markers. We found that BMP signals interfered with FGFs-induced ERK phosphorylation and neuro-caudalisation. This inhibition of BMP signals would involve controlling the expression of Flrt3, a positive regulator of FGF signalling. In addition, we found that Flrt3 got and lost functions restrained and amplified the expression of the forebrain marker gene, respectively. 

Conclusions: These findings suggest that BMP signals can downregulate the anterior nerve formation by limiting Flrt3 expression to downregulate the FGF pathway, revealing the stage-specific function of the BMP signal pathway and its new role in neural development.