Box 3.1 Gene logic

The analysis of gene regulation in animal development has given rise to a number of terms to describe the nature of regulatory interactions. Because the concepts behind these terms are fundamental to understanding genetic logic, it is important to understand the terms and the genetic tests used to define them.

To determine the hierarchical relationships among a set of genes, genetic tests are used to assess the relationships between any two members of the hierarchy. The first question is whether one gene depends on another for proper expression. If the expression of a gene is found to be dependent on another, the first gene is often said to be "downstream" of its "upstream" regulator. The regulatory dependence for expression can either be positive or negative, meaning that a given downstream gene may be dependent on a regulator for its activation or repression.

Another important distinction is whether the expression of the downstream gene depends on one or many regulators. This issue addresses the criterion of necessity versus sufficiency. A regulator may be required for expression of a downstream gene (necessary), but may not be capable of activating gene expression on its own (not sufficient).

Finally, as more potential components of a hierarchy are examined, evidence may accumulate regarding whether a particular interaction may be direct or indirect. If the expression of a downstream gene is affected by multiple upstream genes, then some upstream genes could potentially exert an effect through other upstream genes; hence, those genes have indirect effects on a given downstream gene.

In practice, the architecture of regulatory hierarchies emerges from the detailed analysis of the dependent/independent relationships of individual gene expression patterns with the function of other candidate members of the hierarchy. The combination of genetic tools for altering gene function, molecular techniques for assaying gene expression, and some knowledge of protein function together enable us to establish whether genes of a given phenotypic class control different steps in a single pathway and whether genes of different classes act sequentially or in parallel during development.

temporal and spatial) picture of gene function and regulatory interactions than does the inspection of terminal phenotypes (Box 3.1).

The study of model organisms such as Drosophila has revealed a few general features of the architecture of genetic regulatory hierarchies underlying developmental programs. First, development is a continuum in which every pattern of gene expression has a preceding causal basis—namely, a previous pattern of gene activities. Second, regulatory information often flows through "nodal points"—key genes that integrate multiple spatial inputs and whose products often control a major feature of the future pattern. For example, the location of organ primordia often requires inputs from anteroposterior and dorsoventral coordinate systems that are integrated by selector genes, which directly control the formation of these primordia. By focusing on the genetic control of such nodal genes, we can simplify and resolve the regulatory logic of networks that might appear quite complicated at the formal genetic level. Third, many genes, particularly components of signaling pathways and transcription factors, are deployed at several stages of development in distinct spatial patterns and are involved in a variety of regulatory hierarchies.

Regulatory logic—pathways, circuits, batteries, feedback loops, networks, and the connectivity of genes

The analysis of regulatory interactions between genes has given rise to a host of commonly used terms, often applied with somewhat broad meanings, to describe the higher-order relationships and connections between genes. Because the liberal use of these terms can obscure the concepts they are intended to represent, we take a moment here to define their use in this book.

Let's start with a pathway. We use this term to describe components that are obligately linked in the transmission of information. Signaling pathways, which may be linear or branched, are composed of components that depend on one or more upstream or downstream components to exert their effects (Fig. 3.3). Multiple structurally related ligands, receptors, or transducers might be able to transmit information in a given pathway.

We define a circuit to be larger than a pathway, encompassing additional components that are not obligately linked (Fig. 3.3). For example, while components of signaling pathways


Regulator Regulator

Pathway A Signal

0 0

Post a comment