Figure 21–5 Regulatory DNA defines the gene expression patterns in development. the genome is the same in a muscle cell as in a skin cell, but different genes are active because these cells express different transcription regulators that bind to gene regulatory elements. For example, transcription regulators in skin cells recognize a regulatory element in gene 1, leading to its activation, whereas a different set of regulators is present in muscle cells, binding to and activating gene 3. transcriptional regulators that activate the expression of gene 2 are present in both cell types.
Small Numbers of conserved cell–cell Signaling pathways coordinate Spatial patterning
Spatial patterning of a developing animal requires that cells become different according to their positions in the embryo, which means that cells must respond to extracellular signals produced by other cells, especially their neighbors. In what is probably the commonest mode of spatial patterning, a group of cells starts out with the same developmental potential, and a signal from cells outside the group then induces one or more members of the group to change their character. This process is called inductive signaling. Generally, the inductive signal is limited in time and space so that only a subset of the cells capable of responding—the cells close to the source of the signal—take on the induced character (Figure 21–6). Some inductive signals depend on cell–cell contact; others act over a longer range and are mediated by molecules that diffuse through the extracellular medium or are transported in the bloodstream (see Figure 15–2).
Most of the known inductive events in animal development are governed by a small number of highly conserved signaling pathways, including transforming growth factor-β (TGFβ), Wnt, Hedgehog, Notch, and receptor tyrosine kinase (RTK) pathways (discussed in Chapter 15). The discovery of the limited vocabulary that developing cells use for intercellular communication has emerged over the past 25 years as one of the great simplifying features of developmental biology.
through combinatorial control and cell Memory, Simple Signals can Generate complex patterns
But how can this small number of signaling pathways generate the huge diversity of cells and patterns? Three kinds of mechanisms are responsible. First, through gene duplication, the basic components of a pathway often come to be encoded by small families of closely related homologous genes. This allows for diversity in the operation of the pathway, according to which family member is employed in a given situation. Notch signaling, for example, may be mediated by Notch1 in one tissue, but by its homolog Notch4 in another. Second, the response of a cell to a given signal protein depends on the other signals that the cell is receiving concurrently (Figure 21–7A). As a result, different combinations of signals can generate a large variety of different responses. Third, and most fundamental, the effect of activating a signaling pathway depends on the previous experiences of the responding cell: past influences leave a lasting mark, registered in the state of the cell’s chromatin and the selection of transcription regulatory proteins and RNA molecules that the cell contains. This cell memory enables cells with different cells directed to new developmental pathway
Figure 21–6 Inductive signaling.
Figure 21–7 Two mechanisms for generating different responses to the same inductive signal. (a) In combinatorial signaling, the effect of a signal depends on the presence of other signals received at the same time. (B) through cell memory, previous signals (or other events) can leave a lasting trace that alters the response to the current signal (see Figure 7–54). the memory trace is represented here in the coloring of the cell nucleus.
feld of cells morphogen gradient forms source of morphogen cellular response to gradient 0.1 mm histories to respond to the same signals differently (Figure 21–7B). Thus, the same few signaling pathways can be used repeatedly at different times and places with different outcomes, so as to generate patterns of unlimited complexity.
Morphogens are Long-range Inductive Signals that exert Graded effects