Building the Body, Building the Brain

Abstract

The body plan of any organism presents a daunting engineering challenge. A single fertilized egg divides multiple times to give rise to a ball of seemingly identical cells which eventually achieves the phenomenal task of forming limbs, heart, eyes and brain. What breaks the symmetry such that particular structures are formed in specifi c regions, each distinct in its organization, appearance, and function? In this review we will focus on the fundamental role of “signaling centers” in this process.

Signaling centers are transient groups of cells that appear at key locations during development. These sites are often at tissue boundaries or where one type of tissue is juxtaposed to another type. A signaling center is a source of “morphogens,” molecules that act to induce patterning in adjacent tissues. As a result of diffusion, the concentration of the morphogen(s) decreases with distance creating a morphogen gradient. Cells in the responding tissue acquire distinct identities because of different concentrations of the morphogen. A signaling center can induce an entire patterned structure adjacent to it and is therefore called an “organizer.” We will bring out how multiple organizers interact to create the complexity of the body and the brain via a common set of mechanisms. In the vertebrate limb, spinal cord, and forebrain, members of four signaling molecule families, Wnt, Bmp, Fgf, and Shh, interact to induce different aspects of patterning in the surrounding tissue. These signaling molecules also regulate each other’s expression via mutual induction or repression. A complex choreography of these four players creates the diverse cell types seen in the body and in the brain.