Building a better brain

A six-layered cerebral cortex is a uniquely mammalian structure and is the center of cognitive function. The processes and genetic controls that govern its development are subjects of intensive study and have captured the attention of many developmental biologists. One major goal in this field is the identification of the factors and pathways that control the generation of precise numbers of the principal cell types within the cerebral cortex:neurons, oligodendrocytes and astrocytes. A second major goal is to understand how these building blocks are targeted to the different structures within the cortex, and how they are interconnected to establish functional networks.

The understanding of the ontogeny of the cerebral cortex requires us to understand not only how this structure is built in a step-by-step fashion, but also how this innate program is designed to interact with environmental influences to promote plasticity. Although this is an immense challenge, we need to have a full understanding of the developmental program of the cortex in order to gain an appreciation of how we think. To borrow a commonly used phrase, understanding the cortex is to understand how we understand.

CorticalDevelopment. FromSpecification to Differentiation presents a concise description of several of the key steps that occur during the development of the cortex. This is the first volume to be published in a two-volume set and concentrates on `early' events in ontogeny – issues relating to cortical cell generation/specification,migration and early differentiation. In this volume, Hohmann has selected a cross-section of what she and many in the field would consider to be the most pertinent and exciting areas in current research on cortical ontogeny.

The book is divided into eight chapters, which have been written by different experts in the field and build upon different themes following a more-or-less temporal course through cortical development. Richard Nowakowski et al. beautifully summarize years of collaborative work on the developmental dynamics of cell proliferation in the cortex. This work led to several key advances in the field, including the description of cell cycle regulation in the generation of cortical cells. Mark Mehler, in the first of two chapters that he contributes, focuses on mechanisms of lineage diversity and the role of the bone morphogenetic proteins, fibroblast growth factors (particularly FGF2), sonic hedgehog and basic helix-loop-helix molecules in this process. In his second chapter, he studies regional patterning and neural subtype specification under both morphogen and transcriptional regulation. These mechanisms serve to create the numerous distinct types of cells that constitute the cortex, and we learn of the relationship of these pathways to neurodegenerative diseases.

Later events in cortical development are covered in the subsequent chapters. For example, Bernd Sutor discusses gap junctions and their possible role in establishing early neuronal circuits, while Marcin Gierdalski and Sharon Juliano provide an overview of neuronglial interactions and their role in neuronal migration. This chapter also covers the reeler pathway (in which reelin is secreted from a small group of cells and influences migration of most or all neurons arriving in the cortex), as well as the authors' own work on the methylazoxy methanol (MAM) model of cortical dysplasia, and its relevance to the reeler pathway. Several of these chapters also discuss the processes and molecules that are important for synaptic development and cortical plasticity. For example, A. Kimberly McAllister discusses neurotrophins and their role in dendritic growth and synaptic plasticity, and Alvin Lyckman and Mriganka Sur discuss neuronal re-wiring plasticity in a fascinating model in which the visual input fibers of a ferret are re-routed to the auditory processing centers. In this model, ferrets are capable of using the re-wired auditory cortex to respond to light as a visual, rather than as an auditory, stimulus. The molecular characterization of this model and its future downstream applications, such as strategies to identify differential gene expression, are discussed. The relevance of the immediate-early genes [such as activin, NARP (neuronal activity regulated pentraxin) and homer], which are activated by an initial cascade of gene expression that is triggered by an extracellular signal, are also discussed in the context of synaptic development and cortical plasticity by Katrin Andreasson and Walter Kaufmann.

Increasingly, successful inquiry in the neurosciences depends on strongly interdisciplinary approaches. The interdisciplinary nature of the chapters is one of the great strengths of this book. However, there is little interrelatedness or synergy developed between many of this book's chapters,despite there being much repetition between many of them. That said, each individual chapter does stand alone and provide a detailed view of the role of each of the highlighted molecules and pathways in the construction of the cerebral cortex. Neurodevelopmental biologists may also notice that there is a paucity of loss-of-function data that is customarily used to support the types of arguments that are presented in this text. An uninitiated developmental biologist might therefore choose a textbook that provides a broader view of these events. In addition, the emphasis on synaptic plasticity in the later chapters does not dovetail well with the issues of embryogenesis that are presented in the book's earlier chapters.

These minor criticisms aside, this book helps fill a void in developmental neurobiology by providing a starting point for researchers and for other more advanced students who are in search of an update by authorities of the field of cortical development. It will also help to educate the reader on a number of different specialties that are key to understanding the pathways that underlie the building of the brain.