Morphogens, patterning centers, and their mechanisms of action

Tissue patterning by gradients of form-generating substances, or ‘morphogens,’ is a fundamental paradigm of developmental biology. Nonetheless, it has been unclear whether classic morphogen gradients pattern the mammalian telencephalon and neocortex, or whether these highly specialized and evolved tissues use entirely unique mechanisms. Recent studies indicate that, like most other tissues, the telencephalon is indeed patterned by classic morphogen gradients. This chapter reviews the history and general principles of morphogen gradients in development, the known sources of morphogens in the developing telencephalon, and the evidence that bone morphogenetic proteins and fibroblast growth factors act as graded morphogens to pattern the dorsal telencephalon and neocortex. It then highlights the unique and complex interactions among morphogens within the dorsal telencephalon, and the roles of morphogen gradients and their interactions in human developmental anomalies, particularly holoprosencephaly.