The Questions of Developmental Biology

Ericson and colleagues (1996) have shown that two periods of Sonic hedgehog signaling
are needed to specify the motor neurons: an early period wherein the cells of the ventrolateral
margin are instructed to become ventral neurons, and a later period (which includes the S phase
of its last cell division) that instructs a ventral neuron to become a motor neuron (rather than an
interneuron). The first decision is probably regulated by the secretion of Sonic hedgehog from the
notochord, while the latter decision is more likely regulated by Sonic hedgehog from the floor
plate cells. Sonic hedgehog appears to specify motor neurons by inducing certain transcription
factors at different concentrations (Ericson et al. 1992; Tanabe et al. 1998; see Figure12.14).
The next decision involves target specificity. If a cell is to become a neuron and,
specifically, a motor neuron, will that motor neuron be one that innervates the thigh, the forelimb,
or the tongue? The anterior-posterior specification of the neural tube is regulated primarily by the
Hox genes from the hindbrain through the spinal cord, and by specific head genes (such as Otx) in
the brain. Within a region of the body, motor neuron specificity is regulated by the cell's age
when it last divides. As discussed in Chapter 12, a neuron's birthday determines which layer of
the cortex it will enter. As the younger cells migrate to the periphery, they must pass through
neurons that differentiated earlier in development. As younger motor neurons migrate through the
region of older motor neurons in the intermediate zone, they express new transcription factors as
a result of a retinoic acid (or other retinoid) signal secreted by the early-born motor neurons
(Sockanathan and Jessell 1998). These transcription factors are encoded by the Lim genes and
are structurally related to those encoded by the Hox genes.
As a result of their differing birthdays and migration patterns, motor neurons form three
major groupings (Landmesser 1978; Hollyday 1980). The cell bodies of the motor neurons
projecting to a single muscle are clustered in a longitudinal column called a "pool." These pools
are grouped together into three larger columns according to their targets. Motor neurons in the
column of Terni (CT) project ventrally into the sympathetic ganglia. Motor neuron pools of the
lateral motor column (LMC) extend to the limb musculature, while those of the medial motor
column (MMC) project to the axial muscles. The lateral and medial motor columns are
subdivided along the mediolateral axis in a manner that correlates with the dorsal-ventral
positions of their respective targets (Figure 13.12; Tosney et al. 1995). This arrangement of motor
neurons is constant throughout the vertebrates.