Embryonic Signalling and Induction

Development is directed by continuous, coordinated communication between cells, not by a fixed, entirely autonomous programme unfolding independently within each cell. The general principles of how cells instruct one another apply across development. The specific molecules and signalling pathways are applied in detail within each organ system's developmental account.

Induction is the process by which one group of cells, the inducer, influences the developmental fate of an adjacent, competent group of cells, the responder. It acts through secreted signalling molecules that alter gene expression within the responding tissue.

Induction is central to essentially every major organ-forming event across the entire course of development. Examples include:

• The notochord induces the overlying ectoderm to thicken into the neural plate, the first step of neurulation.
• The optic vesicle, an outgrowth of the developing forebrain, induces the overlying surface ectoderm to form the lens placode, and subsequently the lens itself. Without this inductive contact, no lens forms, regardless of whether the surrounding orbital structures develop normally.
• Reciprocal induction between epithelium and the surrounding mesenchyme drives the branching, tree-like growth of several organs, most notably the lung, kidney, and salivary glands. Signals pass in both directions between the two tissue types repeatedly as branching proceeds.

Induction is frequently sequential and cascading. One inductive event produces a tissue that itself becomes the inducer for the next structure, so a single early signal can set off a long chain of dependent formation events.

This cascading property is why a disruption early in a developmental sequence tends to produce effects that propagate forward. Every subsequent structure that depended on induction from the disrupted tissue fails to form correctly in turn.

Competence is the capacity of a responding tissue to react appropriately to a given inductive signal. The same signal, presented to two different tissues or to the same tissue at two different developmental times, can produce entirely different outcomes, or no response at all. The result depends on the competence of the receiving tissue.

Competence is not fixed or permanent. It changes over developmental time as a tissue's own internal gene expression state changes. A tissue is therefore typically competent to respond to a specific inductive signal only during a limited developmental window.

This time-limited competence is one underlying mechanism of critical periods of development. A signal arriving before or after the tissue's window of competence will fail to produce the normal outcome, even though the signal and the tissue may each be entirely normal in isolation.

Pattern formation is the process by which individual cells within a developing tissue acquire positional information, an internal sense of where they are relative to the rest of the embryo or organ. This allows structures to form with the correct proportions, correct number of parts, and correct orientation relative to the body axes.

Pattern formation depends substantially on morphogens, secreted signalling molecules that diffuse away from a localised source and form a concentration gradient across a field of responding cells.

Cells in the field interpret their local concentration of the morphogen. Different concentration thresholds trigger different developmental responses, so a single gradient can specify multiple distinct cell fates arranged in correct spatial order across the tissue.

This gradient-based mechanism is central to patterning the developing limb, in which morphogen gradients specify the identity of individual digits. It also patterns the neural tube along both its dorsal to ventral and cranial to caudal axes.

A relatively small number of signalling molecule families are reused repeatedly across many organ systems and developmental stages throughout the embryo. Each organ does not invent an entirely novel signalling mechanism. Recognising that the same families recur is a more efficient way of understanding developmental signalling than memorising each organ's signalling in isolation.

The recurring families are:

• the fibroblast growth factor family, heavily involved in limb outgrowth and branching organogenesis
• the sonic hedgehog pathway, central to left to right axis determination, ventral neural tube patterning, and limb digit patterning
• the bone morphogenetic protein family, involved in dorsal neural tube patterning and skeletal formation
• the Wnt signalling family, broadly involved in axis formation and tissue patterning across many organ systems

The specific role each family plays differs from one organ system to the next.

A relatively small number of signalling pathways are reused across many organs. A mutation in a single signalling pathway gene therefore frequently produces a malformation syndrome involving multiple, seemingly unrelated organ systems simultaneously, not a single isolated anomaly. The same disrupted signal was required at several distinct points across development.

This is the mechanistic reason many recognised genetic malformation syndromes present with a consistent, recognisable combination of anomalies spanning limb, craniofacial, and internal organ systems together, rather than a single defect confined to one structure.