Neurons are almost always produced in association with glial cells, which pro- vide a supporting framework and create an enclosed, protected environment in which the neurons can perform their functions. Both cell types, in all animals,
25 mm cell body
dendrites receive synaptic inputs
axon (less than 1 mm to more than 1 m in length)
terminal branches of axon make synapses on target cells
Figure 22–93A typical neuron of a vertebrate. The arrows indicate the
direction in which signals are conveyed. The neuron shown is from the retina of a monkey. The longest and largest neurons in a human extend for about 1 million mm and have an axon diameter of 15 mm. (Drawing of neuron from B.B. Boycott, in Essays on the Nervous System [R. Bellairs and E.G. Gray, eds.]. Oxford, UK: Clarendon Press, 1974.)
Figure 22–94The complex organization of nerve cell connections. This drawing
depicts a section through a small part of a mammalian brain—the olfactory bulb of a dog, stained by the Golgi technique. The black objects are neurons; the thin lines are axons and dendrites, through which the various sets of neurons are interconnected according to precise rules. (From C. Golgi, Riv. sper. freniat. Reggio-Emilia 1:405-425, 1875; reproduced in M. Jacobson,
Developmental Neurobiology, 3rd ed. New York: Plenum, 1992.)
develop from the ectoderm, usually as sister cells or cousins derived from a common precursor. Thus, in vertebrates, the neurons and glial cells of the cen- tral nervous system (including the spinal cord, the brain, and the retina of the eye) derive from the part of the ectoderm that rolls up to form the neural tube, while those of the peripheral nervous system derive mainly from the neural crest (Figure 22–96).
The neural tube, with which we shall be mainly concerned, consists initially of a single-layered epithelium (Figure 22–97). The epithelial cells are the pro- genitors of the neurons and glia. As these cell types are generated, the epithe- lium becomes thickened and transformed into a more complex structure. As dis- cussed earlier, Delta–Notch signaling controls the differentiation of the progen- itor cells into neurons: the nascent neurons express Delta, and thereby inhibit their neighbors from differentiating into neurons at the same time. This ensures that the progenitors do not all differentiate simultaneously but remain as a dividing cell population from which further neurons can be generated. The pro- genitor and, later, glial cells also maintain the cohesiveness of the epithelium and form a scaffolding that spans its thickness. Along and between these tall cells, like animals amid the trees of the forest, the new-born neurons migrate, find their resting places, mature, and send out their axons and dendrites (Figure 22–98).
Signal proteins secreted from the ventral and dorsal sides of the neural tube act as opposing morphogens, causing neurons born at different dorsoventral levels to express different gene regulatory proteins (see Figure 22–80). There are differences along the head-to-tail axis as well, reflecting the anteroposterior pat- tern of expression of Hox genes and the actions of yet other morphogens. More- over, just as in Drosophila, neurons continue to be generated in each region of the central nervous system over many days, weeks, or even months, and this gives rise to still greater diversity, because the cells adopt different characters
outgrowth of axons and dendrites
genesis of neurons refinement of synaptic connections
Figure 22–95The three phases of neural development.
neural folds (neural tube not yet closed)
blood vessel somite placodes of cranial sensory ganglia eye nasal placode heart ear placode/ vesicle neural tube neural crest
Figure 22–96Diagram of a 2-day chick embryo, showing the origins of the nervous system. The neural tube (light green) has already closed,
except at the tail end, and lies internally, beneath the ectoderm, of which it was originally a part (see Figure 22–78). The neural crest (red) lies dorsally just beneath the ectoderm, in or above the roof of the neural tube. In addition, thickenings, or placodes (dark green), in the ectoderm of the head give rise to some of the sensory transducer cells and neurons of that region, including those of the ear and the nose. The cells of the retina of the eye, by contrast, originate as part of the neural tube.
according to their “birthday”—the time of the terminal mitosis that marks the beginning of neuronal differentiation (Figure 22–99). When progenitor cells are taken from an embryonic mouse brain and maintained in culture for several days, individually isolated from their normal surroundings, they go through much the same program as in the intact tissue. That is, they divide repeatedly, producing pairs of daughters that frequently adopt different fates, such that one remains as a dividing progenitor while the other becomes committed to differ- entiate.
The successive divisions throw off a sequence of different neuronal and glial cell types, according to a more-or-less regular timetable. This implies that the progenitors themselves must autonomously change their intrinsic character from one cell generation to the next. The molecular mechanism of this progres- sive change is unknown, just as it is in other cell types where similar slow changes occur.