Building a Human in Space and Time: How Biological Information Organizes Matter into a Human Being

Within just a few weeks, that single cell gives rise to billions of cells that organize themselves into tissues, organs and, ultimately, an entire human body.

How is this possible?

Throughout embryonic development, cells constantly receive molecular signals telling them what to become. But receiving a signal is not enough.

A cell can only respond if it is competent to do so.

At the molecular level, competence means that a cell possesses the machinery required to interpret a developmental signal. This includes expressing the appropriate receptors that detect the signal while also maintaining an epigenetic landscape in which the genes required to respond remain accessible for activation. If either requirement is missing, the signal may still be present, but the cell will not respond.

Cell competence is therefore not an abstract concept. It is a molecular property that determines which signals a cell can interpret, and ultimately, what that cell is capable of becoming.

Two of the most elegant examples of cell competence illustrate that it is regulated both in time and in space.

The first elegant example of cell competence comes from the developing mammalian cerebral cortex.

The neural stem cells lining the ventricular surface of the embryonic brain give rise to different types of neurons at different developmental time points. Remarkably, a single population of stem cells first generates one class of neurons and, later in development, another.

The mammalian cerebral cortex consists of six highly organized neuronal layers. Remarkably, all of these layers are generated from the same neural stem cell population.

How is this possible?

The answer lies in temporal competence, the gradual change in a cell's competence over developmental time.

As development progresses, neural stem cells gradually lose the competence to execute earlier developmental programs while acquiring the competence to execute later ones. Early during development, they generate the neurons that populate the deep cortical layers. A few days later, the very same stem cells begin producing the neurons that populate the upper cortical layers instead.

This principle was demonstrated beautifully in a series of classical transplantation experiments.

When neural stem cells from an early embryonic brain were transplanted into a later-stage brain, they responded to the signals present in their new environment and generated the later-born cortical neurons.

The opposite experiment produced a very different result.

When stem cells from a later embryonic brain were transplanted into an earlier brain, they no longer responded to the signals that normally generate the early-born neurons.

In other words, the stem cells had lost the competence to execute the earlier developmental program. Although the molecular signals were still present, the cells were no longer capable of interpreting them.