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Transcriptomic divergence of network hubs in the prenatal human brain
Stuart Oldham1,2, Gareth Ball3,4
1Developmental Imaging, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Communications Biology
|November 18, 2025
Summary
This study reveals how early gene expression in the prenatal brain shapes complex human brain networks. Researchers found specific genes in mid-gestation correlate with the formation of crucial brain hubs present at birth.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Human brain connectivity features highly connected hub regions, influenced by genetics.
- The molecular mechanisms guiding the formation of these brain hubs are not well understood.
Purpose of the Study:
- To investigate the molecular factors associated with brain network hub formation during mid-gestation.
- To link prenatal gene expression patterns to neonatal brain connectome architecture.
Main Methods:
- Combined high-resolution diffusion MRI data from 208 neonates with prenatal gene expression data.
- Mapped neonatal structural hubs to the µBrain prenatal digital brain atlas.
- Performed transcriptomic analysis to identify differentially expressed genes in network hubs.
Main Results:
- Identified robust hub architecture in the neonatal brain connectome.
- Found differential gene expression in network hubs at mid-gestation, with key genes expressed in the subplate and intermediate zones.
- Hub-associated genes are linked to early neuronal circuitry, cortical expansion, interhemispheric connectivity, and neurodevelopmental disorders.
Conclusions:
- Prenatal gene expression programs significantly shape brain network connectivity from mid-gestation.
- Identified specific prenatal transcriptomic signatures associated with neonatal brain network hubs.
- Early molecular events are critical for establishing the foundational architecture of the human brain connectome.
Related Concept Videos
01:10Transcription
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
02:35Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:17Transcription
Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
01:05Cerebral Hemispheres
The human brain, a complex organ, is functionally divided into two cerebral hemispheres—left and right. These hemispheres are interconnected by a structure of paramount importance, the corpus callosum. This substantial bundle of neural fibers is not just a bridge between the hemispheres but a crucial element for the brain's comprehensive functioning. It enables efficient communication between the two hemispheres, allowing each side of the brain to control and receive sensory and motor...