Arsić Dejan, Beasley Spencer W, Sullivan Michael J
Children's Cancer and Developmental Genetics Research Group, Department of Paediatrics, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
J Paediatr Child Health. 2007 Jun;43(6):421-3. doi: 10.1111/j.1440-1754.2007.01104.x.
Embryonic and fetal development is a highly complex process choreographed by several families of genes that regulate early development of the embryo. Disruption in the structure and/or function of developmental genes produces morphogenic errors of development. One such family is the Hedgehog (Hh) signalling pathway, which plays an important role in the embryonal development of both invertebrates and vertebrates, including normal development of the brain, eye, limbs, foregut and its derivatives. Disruption of the Sonic hedgehog expression during critical periods of development is associated with developmental disorders of the brain, namely, holoprosencephaly, and the VATER association. Inappropriate activation of the pathway in post-embryonic development has been demonstrated in several human malignancies, including those of the brain and skin, both in children and adults. Specific inhibition of Hh signalling in these tumours inhibits growth of a wide range of malignancies. This demonstrates a requirement for Hh signalling in these tumours. These observations suggest that a better understanding of the genetic control of morphogenesis can ultimately provide us with greater knowledge of how congenital structural abnormalities occur, as well as the processes that lead to several childhood and other tumours. There may be a closer relationship between embryogenesis and oncogenesis than previously realised.
胚胎和胎儿发育是一个高度复杂的过程，由几个调控胚胎早期发育的基因家族精心编排。发育基因的结构和/或功能破坏会产生发育的形态发生错误。其中一个家族是刺猬（Hh）信号通路，它在无脊椎动物和脊椎动物的胚胎发育中都起着重要作用，包括大脑、眼睛、四肢、前肠及其衍生物的正常发育。在发育的关键时期，音猬因子表达的破坏与大脑发育障碍有关，即全前脑畸形和VATER联合征。在包括儿童和成人的脑和皮肤等几种人类恶性肿瘤中，已证实该通路在胚胎后发育中存在不适当激活。在这些肿瘤中特异性抑制Hh信号可抑制多种恶性肿瘤的生长。这表明这些肿瘤中需要Hh信号。这些观察结果表明，更好地理解形态发生的遗传控制最终可以让我们更深入地了解先天性结构异常是如何发生的，以及导致几种儿童期和其他肿瘤的过程。胚胎发生和肿瘤发生之间的关系可能比以前认识到的更为密切。
