Eroglu Binnur, Wang Guanghu, Tu Naxin, Sun Xutong, Mivechi Nahid F
Center for Molecular Chaperone/Radiobiology and Cancer Virology, Medical College of Georgia, Augusta, Georgia, USA.
Dev Dyn. 2006 Oct;235(10):2722-35. doi: 10.1002/dvdy.20911.
Brg1 is a member of the SWI/SNF chromatin-remodeling complex, and in some organisms Brg1 has been shown to interact with beta-catenin and positively control the TCF/LEF transcription factor that is located downstream of the Wnt signal transduction pathway. During development, TCF/LEF activity is critical during neurogenesis and head induction. In zebrafish, Brg1-deficient embryos exhibit retinal cell differentiation and eye defects; however, the role of Brg1 in neurogenesis and neural crest cell induction remains elusive. We used zebrafish deficient in Brg1 (yng) or Brg1 specific-morpholino oligonucleotide-mediated knockdown to analyze the embryonic requirements of Brg1. Our results indicate that reduction in Brg1 expression leads to the expansion of the forebrain-specific transcription factor, six3, and marked reduction in expression of the mid/hind-brain boundary and hind-brain genes, engrailed2 and krox20, respectively. At 12 hpf, the expression of neural crest specifiers are severely affected in Brg1-morpholino-injected embryos. These results suggest that Brg1 is involved in neural crest induction, which is critical for the development of neurons, glia, pigment cells, and craniofacial structures. Brg1 is a maternal factor, and brg1-deficient embryos bearing the yng mutation derived from heterozygote intercrosses exhibit lesser effects on neural crest-specific gene expression, but show defects in neurogenesis and neural crest cell differentiation. This is exhibited by the aberrant brain patterning, a reduction in the sensory neurons, and craniofacial defects. These results further elucidate the critical role for Brg1 in neurogenesis, neural crest induction, and differentiation.
Brg1是SWI/SNF染色质重塑复合体的成员，在一些生物体中，Brg1已被证明与β-连环蛋白相互作用，并正向调控位于Wnt信号转导通路下游的TCF/LEF转录因子。在发育过程中，TCF/LEF活性在神经发生和头部诱导过程中至关重要。在斑马鱼中，缺乏Brg1的胚胎表现出视网膜细胞分化和眼睛缺陷；然而，Brg1在神经发生和神经嵴细胞诱导中的作用仍不清楚。我们使用缺乏Brg1的斑马鱼（yng）或Brg1特异性吗啉代寡核苷酸介导的敲低来分析Brg1在胚胎中的需求。我们的结果表明，Brg1表达的降低导致前脑特异性转录因子six3的扩增，以及中/后脑边界和后脑基因engrailed2和krox20表达的显著降低。在12 hpf时，注射Brg1吗啉代的胚胎中神经嵴特异性因子的表达受到严重影响。这些结果表明，Brg1参与神经嵴诱导，这对神经元、神经胶质细胞、色素细胞和颅面结构的发育至关重要。Brg1是一种母体因子，来自杂合子杂交的携带yng突变的brg1缺陷胚胎对神经嵴特异性基因表达的影响较小，但在神经发生和神经嵴细胞分化方面表现出缺陷。这表现为异常的脑模式、感觉神经元的减少和颅面缺陷。这些结果进一步阐明了Brg1在神经发生、神经嵴诱导和分化中的关键作用。
