Transgenic labeling of a single type of retinal ganglion cell in the mouse retina. Colors represent depth through the retina, with axons at the surface in blue and the deepest dendrites in red. Incompletely understood guidance mechanisms result in J-RGC dendrites “pointing” ventrally, resulting in their preferential response to ventral motion. J-RGC axons are guided to the optic nerve through which they travel to the rest of the brain. (Reproduced, with permission, from Jinyue Liu and Joshua Sanes. Reproduced, with permission, from Journal of Neuroscience. Cover of issue 37(50), December 13, 2017; for Liu J, Sanes JR. 2017. Cellular and molecular analysis of dendritic morphogenesis in a retinal cell type that senses color contrast and ventral motion. J Neurosci 37:12247–12262.)
THE INNUMERABLE BEHAVIORS controlled by the mature nervous system—our thoughts, perceptions, decisions, emotions, and actions—depend on precise patterns of synaptic connectivity among the billions of neurons in our brain and spinal cord. These connections form during embryonic and early postnatal life but can then be remodeled throughout life. In this section, we describe how the nervous system develops and matures.
The history of developmental neurobiology is long and illustrious. Nearly 150 years ago, Santiago Ramón y Cajal undertook a comprehensive series of anatomical studies on the structure and organization of the nervous system and then set out to probe its development. The only method available to him was light microscopic analysis of fixed tissue, but from his observations, he deduced many developmental principles that are still recognized as correct. During the first half of the 20th century, other anatomists followed in his footsteps. Progress then accelerated as new methods became available—first electrophysiology and electron microscopy and, more recently, molecular biology, genetics, and live imaging. We now know a great deal about molecules that determine how nerve cells acquire their identities, how they extend axons to target cells, and how these axons choose appropriate synaptic partners once they have arrived at their destinations.
It is useful to divide the numerous steps that compose neural development into three epochs, which are conceptually distinct even though they overlap temporally to some extent. The first, beginning at the earliest stages of embryogenesis, leads to the generation and differentiation of neurons and glia. One can think of this epoch as devoted to producing the components from which neural circuits will be assembled: the hardware. These steps depend on the expression of particular genes at particular times and places. Some of the molecules that control these spatial and temporal patterns are transcription factors that act at the level of DNA to regulate gene expression. They act within the differentiating cells and are therefore called cell-autonomous factors. Other factors, called cell non-autonomous, include cell surface and secreted molecules that arise from other cells. They act by binding to receptors on the differentiating cells and generating signals that regulate the activity of ...