Gradients in the Brain: The Control of the Development of Form and Function in the Cerebral Cortex
Open accessAbstract
In the developing brain, gradients are commonly used to divide neurogenic regions into distinct functional domains. In this article, we discuss the functions of morphogen and gene expression gradients in the assembly of the nervous system in the context of the development of the cerebral cortex. The cerebral cortex is a mammal-specific region of the forebrain that functions at the top of the neural hierarchy to process and interpret sensory information, plan and organize tasks, and to control motor functions. The mature cerebral cortex is a modular structure, consisting of anatomically and functionally distinct areas. Those areas of neurons are generated from a uniform neuroepithelial sheet by two forms of gradients: graded extracellular signals and a set of transcription factor gradients operating across the field of neocortical stem cells. Fgf signaling from the rostral pole of the cerebral cortex sets up gradients of expression of transcription factors by both activating and repressing gene expression. However, in contrast to the spinal cord and the early Drosophila embryo, these gradients are not subsequently resolved into molecularly distinct domains of gene expression. Instead, graded information in stem cells is translated into discrete, region-specific gene expression in the postmitotic neuronal progeny of the stem cells.
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More rostrally- than caudally-enriched genes were found in nearly every cortical layer, whereas two studies of prenatal mouse brain identified more or comparable caudally-enriched genes, indicating potential species differences related to areal patterning.
“Interestingly, we find more rostrally- than caudally-enriched genes in nearly every cortical layer (Fig. 5h), whereas two studies of gradient expression in prenatal mouse brain identified more49 or comparable51 caudally-enriched genes, indicating potential species differences related to areal patterning.”
From Transcriptional landscape of the prenatal human brain (2014) · cites this paper as [49]
Cortical patterning is likely a result of intrinsic signaling, controlled in part by graded expression of transcription factors during early cortical development, followed by extrinsic signaling from thalamic afferents after the start of corticogenesis.
“Cortical patterning is likely a result of intrinsic signaling, controlled in part by graded expression of transcription factors during early cortical development, followed by extrinsic signaling from thalamic afferents after the start of corticogenesis46–49.”
From Transcriptional landscape of the prenatal human brain (2014) · cites this paper as [49]
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- Authors
- Sansom, S. N., & Livesey, F. J.
- Affiliations
- University of Cambridge (GB)
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-08-01
- Volume
- 1
- Issue
- 2
- Pages
- a002519-a002519
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC2742095
- OpenAlex
- W2105287799
- Cited by
- 148
- References
- 78
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 8 · 2016: 9 · 2015: 9 · 2014: 15 · 2013: 19 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- cortical development, morphogen gradients, gene expression gradients, FGF signaling, neurogenesis, regionalization
- MeSH terms
- Animals, Brain, Cerebral Cortex, Drosophila, Fibroblast Growth Factors, Models, Biological, Motor Cortex, Nervous System, Neurons, Spinal Cord, Stem Cells, Transcription Factors, Gene Expression Regulation, Developmental, Mice
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