Switched-on Sonic hedgehog: a gene whose activity extends beyond fetal development--to oncogenesis

Abstract

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.