The Questions of Developmental Biology

As we saw in Chapter 12, the axon has its own locomotory apparatus, which resides in the growth
cone. The growth cone can respond to the same types of signals that migrating cells can sense.
The cues for axonal migration, moreover, may be even more specific than those used to guide
certain cell types to particular areas. Each of the 10 11 neurons in the human brain has the potential
to interact specifically with thousands of other neurons, and a large neuron (such as a Purkinje
cell or motor neuron) can receive input from more than 10 5 other cells (Figure 13.11; Gershon et
al. 1985). Understanding the generation of this stunningly ordered complexity is one of the
greatest challenges to modern science.
Goodman and Doe (1993) list eight stages of
neurogenesis:
1. The induction and patterning of a neuronforming
(neurogenic) region
2. The birth and migration of neurons and glia
3. The specification of cell fates
4. The guidance of axonal growth cones to specific targets
5. The formation of synaptic connections
6. The binding of trophic factors for survival and differentiation
7. The competitive rearrangement of functional synapses
8. Continued synaptic plasticity during the organism's lifetime
The first two of these processes were the topics of the previous chapter. Here, we continue our
investigation of the processes of neural development.
The Generation of Neuronal Diversity
Neurons are specified in a hierarchical manner. The first decision is whether a given cell
is to become a neuron or epidermis. If the cell is to become a neuron, the next decision is what
type of neuron it will be: whether it is to become a motor neuron, a sensory neuron, a
commissural neuron, or some other type. After this fate is determined, still another decision gives
the neuron a specific target. To illustrate this process of progressive specification, we will focus
on the motor neurons of vertebrates.
Vertebrates form a dorsal neural tube by blocking a BMP signal, and the specification of
neural (as opposed to glial or epidermal) fate is accomplished through the Notch-Delta pathway
(see Chapter 12). The specification of the type of neuron appears to be controlled by the position
of the neuronal precursor within the neural tube and by its birthday. As described in Chapter 12,
neurons at the ventrolateral margin of the vertebrate neural tube become the motor neurons, while
different interneurons are derived from cells in the dorsal region of the tube. Since the grafting of
floor plate or notochord cells (which secrete Sonic hedgehog protein) to lateral areas can
respecify dorsolateral cells as motor neurons, the decision as to type of neuron is probably a
function of the cell's position relative to the floor plate.