The Expression Of STAT3 In The Developing Nervous System Of Mouse And The Relationship With The NTD

The development of neural tube is an important embryologic event involved in the primordium establishment of the central nervous system. During this process, nervous system can't develop normally until the neural plate closes on time accurately, or the neural tube defect (NTD) would occur. Nowadays, the studies of the developmental neurobiology have focused on the molecular mechanisms of the development of nervous system. Some studies have revealed that signal transducer and activator of transcription factor-3 (STAT3) was expressed in the developing brain area strongly at embryo 9.5d (E9.5d), when neural tube closed. Could it be possibe that STAT3 may be involved in the closure of neural tube and its changes were related with NTD?Following the closure, neuroepithelium continued to prolife, differentiate and migrate, and prosencephalon, mesencephalons and rhombencephalon appeared in the anterior region of neural tube. The proliferation, differentiation and migration of the neuroepithelium are essential for the structural formation and functional establishment of the nervous system. Recent studies have revealed that a number of genes participated in the regulation and control of development of the central nervous system and some environmental factors exert their functions via these genes as well. As a transcription factor, STAT3 participated in the control of their target genes' expression and forms a complicated network together with other transcription factors. Could the expression of STAT3 protein in the neuroepithelium suggest that STAT3 may contribute to the proliferation, differentiation and migration of neuroepithelium by promoting the expression of its target genes?Fibroblast growth factors (FGFs) have recently been implicated as regulators of many key processes during early neural development. Studies in avian embryos have shown that FGF can induce the development of neural tissue. FGF8 has been shown to be expressed only during the early embryonic proliferation and neurogenesis, suggested a role it played in the early neural development and differentiation. It is known that FGF is one of the growth factors which can activate STATs. FGF2 can activate STAT3, which suggested that FGF8 could activate STAT3. Could both of them be involved in the closure of neural tube? However, at present the studies about the gene expression, regulation and control of the complicated process of the nervous system's development have just started, especially those relating to neural tube closure and neural tube defect (NTD). And very little is known about the correlative genes and relevant pathways.In the present study, the expression and changes of STAT3 mRNA and protein were observed during the embryonic development using the whole-mount embryo in situ hybridization, immunohistochemistry etc; the changes of STAT3 mRNA expression were also observed in NTD by establishing a model of retinoic acid (RA)-induced NTD through adminisitrating overdose RA; the expression of FGF8 mRNA during neurulation and expression changes in NTD were also examined. Finally, a comparison of the expression and ralationship between the expression changes of FGF8 mRNA and STAT3 mRNA were carried out in order to investigate the roles of STAT3 in the development of neuroepithelium and the closure of neural tube, trying to reveal the function of this pathway and possible molecular mechanism in the developing nervous system. The results are as follows:â… .The expression of STAT3 in the developing nervous system of mouse1. The expression of STAT3 mRNA was detected from E8.75d to E11.5d by whole-mount embryo in situ hybridization staining. At E8.75d, STAT3 mRNA was hardly detected in the embryo; at E9.5d, STAT3 mRNA increased in the prosencephalon dramatically with the closure of neural tube; at E10.5d, STAT3 mRNA was observed in the mesencephalon; at E11.5d, STAT3 mRNA was limited to a narrow region in the metencephalon. The expression of STAT3 mRNA in the embryonic nerve tissue, especially the expression and spatio-temporal changes of STAT3...