Section of Molecular, Cell and Developmental Biology, Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America.
PLoS One. 2013;8(3):e59533. doi: 10.1371/journal.pone.0059533. Epub 2013 Mar 21.
In human, mutation of the transcription factor SATB2 causes severe defects to the palate and jaw. The expression and sequence of SATB2 is highly conserved across vertebrate species, including zebrafish. We sought to understand the regulation of satb2 using the zebrafish model system. Due to the normal expression domains of satb2, we analyzed satb2 expression in mutants with disrupted Hh signaling or defective ventral patterning. While satb2 expression appears independent of Edn1 signaling, appropriate expression requires Shha, Smo, Smad5 and Hand2 function. Transplantation experiments show that neural crest cells receive both Bmp and Hh signaling to induce satb2 expression. Dorsomorphin- and cyclopamine-mediated inhibition of Bmp and Hh signaling, respectively, suggests that proper satb2 expression requires a relatively earlier Bmp signal and a later Hh signal. We propose that Bmp signaling establishes competence for the neural crest to respond to Hh signaling, thus inducing satb2 expression.
在人类中，转录因子 SATB2 的突变会导致 palate 和 jaw 严重缺陷。SATB2 的表达和序列在包括斑马鱼在内的脊椎动物物种中高度保守。我们试图利用斑马鱼模型系统来理解 satb2 的调控。由于 satb2 的正常表达域，我们分析了 HH 信号中断或腹侧模式缺陷突变体中的 satb2 表达。虽然 satb2 的表达似乎独立于 Edn1 信号，但适当的表达需要 Shha、Smo、Smad5 和 Hand2 的功能。移植实验表明，神经嵴细胞同时接收 Bmp 和 HH 信号以诱导 satb2 的表达。Dorsomorphin 和 cyclopamine 分别抑制 Bmp 和 HH 信号，表明适当的 satb2 表达需要相对较早的 Bmp 信号和较晚的 HH 信号。我们提出，Bmp 信号为神经嵴细胞对 HH 信号做出反应建立了能力，从而诱导 satb2 的表达。
