胚胎能自我修复“器官”以预防其畸形发育

　　牙齿发育早期的Barx1遗传基因的表现（红色部分）

　　据媒体报道，《美国国家科学院院刊》发表了伦敦国王大学齿科学院的一项研究，这项研究阐述了当胚胎器官在子宫内生长异常的时候，骨形态发生蛋白通路作为关键的发育通路负责确保器官的自我修复。受精卵通过胚胎发育过程生长成为胚胎，最后长成为人类。这个转变中的许多过程都是非常复杂的也存在发生差错的可能。胚胎发育过程的差错会导致先天畸形，先天畸形占到人类出生总人数的3%-5%，但是相对于胚胎发育过程的复杂性，这个低的比例事实上是非常让人惊奇的。

　　为了探索如何避免潜在的缺陷，国王大学的研究团队观察了发育中老鼠胚胎的不同形状牙齿。他们使一种叫做“Barx1”的遗传基因产生了基因变异，该基因决定臼齿的发育。然而，这个基因功能的缺失并没有如预期的一样导致臼齿的变异，在胚胎的发育过程中臼齿的发育完全的停滞了。这种停滞是由于骨形态发生蛋白通路的减少造成的，这些通道先前已经得到确认是胚胎发育的中枢。在这个停滞时期，骨形态发生蛋白非常活跃，最终稳定的上升到正常临界值之上的水平，随后的臼齿发育加速赶上胚胎其它部分的发育。

　　研究人员表示，器官发育自主停滞的行为是胚胎修正细胞传输信号错误的方法，错误的细胞信号或许会导致畸形发育。国王齿科学院颅面发育部门的保罗-夏普教授说：“发育停滞可能是一种普遍的机制，这将机制帮助发育中的组织和器官自我修复在复杂的交互作用中产生的任何细微错误，正是这种交互作用推动所有的发育过程。

　　他说，我们现在想探索和了解在这个过程背后的分子机制，这将帮助我们了解这个机制是否也存在于其它器官的发育过程。如果我们能够了解它是如何工作的，我们将对人类先天缺陷的形成有深入的了解。

　　Developmental stalling and organ-autonomous regulation of morphogenesis

　　Isabelle Miletich， Wei-Yuan Yu, Ruofang Zhang, Kai Yang, Simone Caixeta de Andrade, Silvia Fontes do A. Pereira, Atsushi Ohazama, Orin B. Mock, Georg Buchnera, Jane Sealbyd, Zoe Webster, Minglian Zhao, Marianna Beie,f, and Paul T. Sharpe

　　Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of Barx1 transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure.