CHAPTER 1

Introduction

What Do We Mean When We Say "Neural Development"?

Development unfolds smoothly over time but can be divided for experimentalanalysis into successive stages, each with its own defining events. Someof these events have clear beginnings and endings, although others may beprotracted, sometimes unexpectedly so. For example, myelination of axonsin the human brain, a key event that supports behavioral development byincreasing the rate of action potential transmission, begins approximately24 weeks after conception and then continues for decades. In general, theearliest events are most easily categorized as discrete stages shared by almostall members of a species, whereas later events are best described as ongoingprocesses, the exact details of which are unique to each brain. This is particularlytrue in long-lived species such as humans, but the inherent ability ofnervous systems to refine neural circuitry across the life span is evident evenin short-lived invertebrates. The neuroscientist Martin Heisenberg and colleagueswere reflecting on data obtained from neuroanatomical studies offruit fly brains, not human brains, when they were inspired to write, "Anindividual's life experience can ... be encoded in the volume of selectedneuropil regions."

What Is in This Book and How to Use It

After a brief presentation of methods (this chapter), an overview of humandevelopment (Chapter 2), and an introduction to animal models (Chapter3), the subsequent chapters consider the molecular mechanisms of selectedearlier and later events (Chapters 4 and 6), neurogenesis (Chapter 5), andformation of synapses (Chapter 7). Glial cells are the focus of Chapter 8.Chapter 9 describes the postembryonic maturation of the nervous systemvia metamorphosis in some species and adolescence in others. In Chapter 10the focus shifts to human intellectual disabilities. This chapter attempts tobuild a case that at least some forms of human intellectual disability reflectreversible differences in developmental processes rather than permanentdeficits. This chapter was inspired by my personal connections with twooutstanding neuroscientists—William T. Greenough at the University of Illinoisat Urbana-Champaign and Linda L. Restifo of the University of Arizona,a researcher who is also a physician. Many other outstanding investigatorswork in this field, but it was Greenough's studies of the fragile X protein inthe context of his life's work on experience-driven brain plasticity and Restifo'sstudies of mental retardation genes in Drosophila that forced me torethink my views on human intellectual disability.

Each chapter has notes. Some provide additional background informationon the topic being discussed. This information may be useful and/orinteresting, but it has been placed in the notes because I believe it is notessential for an understanding of neural development. The notes are probablymost helpful if they are consulted the first time you read the chapter.Some notes link specific results recounted in the text to specific references.The full references can be found in the chapter-by-chapter reference liststhat appear at the end of the book. These reference lists also include pertinentreviews and commentaries that provide additional context if you areinterested in the history of developmental neuroscience. Short chapter-by-chapterlists of trustworthy online resources can also be found at the end ofthe book. These are intended to provide additional graphic material andtechnical details as well as links to selected patient information web sites.This material is also nonessential. It is included to allow you to follow up aspecific interest, either as you read or in the future.

Students who want to go further will find that there are numerous pointsof entry into the research literature. The student can begin with the end-of-chaptersuggestions for Investigative Reading. Each of these readings is introducedby a short question based on the chapter. The answer to the question(one answer; the student may well come up with a superior alternative) iscontained in the recommended reading. Students are encouraged to try toanswer the questions on their own before going online to retrieve the article.Note that only partial citations are provided at the end of each chapter.This is because the titles of the articles often give the answers away! Thejournal articles listed in the Investigative Reading sections are freely accessibleonline, and full citations are provided at the end of the book.

This text is designed to provide a concise introduction to nervous systemdevelopment. This goal will be achieved, in part, by a nearly exclusive focuson the central nervous system (the brain and spinal cord in vertebrates, thebrain and nerve cord in invertebrates). We'll venture into the peripheralnervous system primarily in Chapter 7, where I use the neuromuscular junctionto describe how synapses form. Topics intentionally shortchanged forthe sake of brevity include the history of embryology, the neural crest, developmentof vertebrate sense organs, and the emerging story of microRNAs(miRNAs) as posttranscriptional regulators of...