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Cited by 585Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationNeuroscience and Neuropharmacology Research

The Control of Neuron Number

Williams, R W, Herrup, K·1988·Annual Review of Neuroscience
DOI 10.1146/annurev.ne.11.030188.002231
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Abstract

In comparing strategies used to control neuron number, we find it useful to view nervous system development as occurring in three phases. The phases overlap--each is a process, not an event. The first phase is the development of a genetic nervous system. This is a nervous system of simple genetic intention, not a blueprint or pile of bricks. Its characteristics are abstract: How many neurons in this stem cell destined to produce, which cells are programmed to die, how much target does this cell need to survive. At the level of the individual, the genetic nervous system is essentially fixed, but over generations it is fluid. As this genetic intent interacts within a world of cells, a real brain appears. A new set of rules only tacitly present in the genome is expressed--the embryonic nervous system emerges. The interaction of its parts defines the shape and size of the nervous system. Neuron numbers are adjusted interactively by changes in proliferative potential and the severity of cell death. Cell fates are established in part through interactions with other cells and with hormones. Glial cell numbers are adjusted to match the neuron populations. This phase of brain development is what the embryologist sees under the microscope. The third and final phase of development begins when the brain starts to function and the animal starts to deal with its world. Small changes in neuron number may occur during this period, but these changes are generally of minor functional importance. At this point, the smaller elements of neuronal organization are refined in shape, number, and distribution. Axons are lost or rearranged; dendrites grow, branch, and retract; synapses are fine-tuned; and finally, receptor densities and transmitter titres are adjusted. Some of these interactions and numerical adjustments continue until the animal dies.

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Crossref · 10.1146/annurev.ne.11.030188.002231

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124 of 124 references verified0 citation errors · 0 not checkable

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  • Across species, the number of neurons and their relative abundance in different brain parts is widely considered a determinant of neural function and behavior.

    “Across species, the number of neurons and their relative abundance in different parts of the brain is widely considered to be a determinant of neural function and, consequently, of behavior (Williams and Herrup, 1988).”

    From The human brain in numbers: a linearly scaled-up primate brain (2009) · cites this paper as Williams and Herrup, 1988

  • Williams and Herrup estimated the human brain has about 85 billion neurons: 12-15 billion in the telencephalon, 70 billion cerebellar granule cells, and fewer than 1 billion in the brainstem.

    “These authors estimated the number of neurons in the human brain at about 85 billion: 12–15 billion in the telencephalon (Shariff, 1953), 70 billion in the cerebellum, as granule cells (based on Lange, 1975), and fewer than 1 billion in the brainstem.”

    From The human brain in numbers: a linearly scaled-up primate brain (2009) · cites this paper as Williams and Herrup (1988)

  • In the central nervous system, overproduction of neurons with ensuing neuronal death is a common mechanism employed by the developing brain to ensure that the appropriate balance of projection and receptive neurons is attained.

    “in the central nervous system overproduction of neurons with ensuing neuronal death is a common mechanism employed by the developing brain to ensure that the appropriate balance of projection and receptive neurons is attained.19, 23, 24, 25”

    From A role for synaptic plasticity in the adolescent development of executive function (2013) · cites this paper as [23]

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Authors
Williams, R. W., & Herrup, K.
Affiliations
Yale University (US)
ORCID
Venue
Annual Review of Neuroscience
Publisher
Annual Reviews
Published
1988-03
Volume
11
Issue
1
Pages
423-453
ISSN
  • 0147-006X (ISSN-L)
  • 1545-4126
DOI
10.1146/annurev.ne.11.030188.002231
OpenAlex
W2162717455
Cited by
585
References
124
Citations by year
2026: 4 · 2025: 11 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 20 · 2020: 13 · 2019: 18 · 2018: 13 · 2017: 26 · 2016: 19 · 2015: 25 · 2014: 32 · 2013: 26 · 2012: 18
FWCI
5.52
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS18381, NS20591)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
neuron number, brain development, embryonic nervous system, cell proliferation, programmed cell death, cell fate determination, synaptic refinement, axon and dendrite development, receptor density
MeSH terms
Animals, Cell Count, Cell Survival, Central Nervous System, Chimera, Neuronal Plasticity, Neurons, Species Specificity, Mice

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