2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
September 2nd, 2025
Version: 1
Children\'s National Research Institute
neuroscience
bioRxiv

Intrinsic Gestational Timing Governs Human Cerebellar Development After Preterm Birth

Sanidas, G.Open in Google Scholar•Simonti, G.Open in Google Scholar•Ghaemmaghami, J.Open in Google Scholar•Woyshner, K.Open in Google Scholar•Vidva, R.Open in Google Scholar•Wolff, N.Open in Google Scholar•Triantafyllou, M.Open in Google Scholar•Lowe, C.Open in Google Scholar•Vij, A.Open in Google Scholar•Pettersen, H. P. S.Open in Google Scholaret al.

Intrinsic biological clocks govern human brain development, but whether these programs recover from early disruption, such as premature birth, remains unknown. The cerebellum, with peak maturation in the last trimester, provides a model to address this challenge. We analyzed an unprecedented combination of in-vivo and postmortem cohorts of human postnatal cerebella spanning 22-42 weeks gestation, integrating longitudinal neuroimaging, spatial transcriptomics, and machine-learning-based histology to capture developmental states inaccessible to experimental models. Gestational age imposed lasting differences in postnatal cerebellar growth, architecture, and molecular programs. Spatially resolved gene expression data revealed lineage-specific rules: granule cells followed an immutable developmental clock, whereas Purkinje cells failed to undergo the maturation-linked reduction in cell numbers, retaining their population but with reduced dendritic complexity, reflected by a thinner molecular layer after early extrauterine transition. These findings redefine prematurity as a state-dependent arrest of intrinsic brain programs and provide a foundation for regenerative and neuroprotective interventions.

Similar Papers

bioRxiv
Wed Sep 03 2025
Neurovascular Large artery dilatation increases the risk for Alzheimer's disease pathology
Alzheimer\'s disease (AD) and related dementia cases are increasing globally, emphasizing the urgent need to clarify disease mechanisms for translational application in diagnoses and treatment. Vascular alterations represent a major pathological feature of AD, and beyond the well-established roles of small vessel disease and large artery atherosclerosis, our group has previously demonstrated that ...
Simpson, D.
•
Morrone, C. D.
•
Wear, D.
•
Khani, A.
...•
Yu, W. H.
bioRxiv
Wed Sep 03 2025
Memory-Related Default-Executive Coupling Across the Lifespan and Associations with Changes in Cognitive Control
Episodic memory and cognitive control declines in aging. The default-executive coupling hypothesis of aging (DECHA) suggests that a neural correlate of cognitive decline in aging is increased functional connectivity (FC) between lateral prefrontal areas and the default mode network. Here, in a lifespan sample (n=552, 6-81years), we tested FC between the left dorsolateral prefrontal cortex (dLPFC) ...
Blakstad, E. G.
•
Sneve, M.
•
Vidal-Pineiro, D.
•
Walhovd, K. B.
...•
Grydeland, H.
bioRxiv
Wed Sep 03 2025
Decoding the dynamics of cognitive control: Insights from reach movements and electroencephalography
The congruency sequence effect (CSE) refers to improved performance in conflict tasks, such as the Eriksen flanker task, when the congruency of the current trial matches that of the preceding one. Although widely attributed to dynamic adjustments in cognitive control, the neural mechanisms and temporal dynamics underlying this effect remain poorly understood. Here, we combined a release-and-press ...
Shoura, M.
•
McNair, K.
•
Nestor, A.
•
Erb, C.
bioRxiv
Wed Sep 03 2025
m6A methylation regulates RNA axonal localisation and translation in developing neurons
Methylation on adenosine N6 (m6A) is an abundant post-transcriptional modification of the RNA that regulates almost the entire lifespan of RNA transcripts, from splicing and nuclear export to RNA stability and translation. Peripheral localisation of RNA is an event common to most cells and especially relevant in neurons where transcripts are trafficked to subcellular compartments to promote growth...
Riccio, A.
•
Martinez De La Cruz, B.
•
Galkin, S.
•
Wang, S.
...•
Jing, Y.
bioRxiv
Wed Sep 03 2025
Single-molecule imaging reveals activity-dependent regulation of Camk2a mRNAs at dendritic spines
Postsynaptic calcium/calmodulin-dependent protein kinase type II (CaMKII) integrates fleeting Ca2+ transients into long-term synaptic potentiation (LTP). A persistent presence of CaMKII at dendritic spines during the maintenance of LTP facilitates the prolongation of synaptic transmission. Yet, it remains unclear how the perpetuation of CaMKII, despite protein turnover, is achieved at dendritic sp...
Hwang, D.-W.
•
Krishnamurthy, K.
•
Nagare, A.
•
Singer, R. H.
•
Das, S.
bioRxiv
Wed Sep 03 2025
Adaptor protein complex 2 (AP2) participates in biogenesis and homeostasis of myelin sheaths in the central nervous system
Myelination of CNS axons requires oligodendrocytes to undergo extensive morphological changes by producing large amounts of myelin membrane with defined protein composition and structure. The formation of myelin sheaths thus involves efficient trafficking and sorting of future myelin constituents via vesicles that fuse with prospective myelin membranes by exocytotic mechanisms. However, the functi...
Siems, S. B.
•
Jung, R. B.
•
Jahn, O.
•
Meschkat, M.
...•
Werner, H. B.
bioRxiv
Wed Sep 03 2025
Mechanisms of perisynaptic astrocyte depolarization in response to neuronal activity
Recent studies show that astrocytic depolarization can be induced at the periphery of cortical somatosensory astrocytes, proposed to be the contact sites between neurons and astrocytes. However, specific mechanisms causing astrocytic depolarization have yet to be confirmed due to limitations in experimental techniques. Here, we constructed a computational whole-cell astrocyte model to assess which...
Nakatani, R. J.
•
De Schutter, E.
bioRxiv
Wed Sep 03 2025
Inflexible center-frequency shifts in neural speech tracking are linked to reading and phonological deficits in developmental dyslexia
Developmental dyslexia is marked by persistent deficits in reading and phonological awareness, potentially linked to atypical neural tracking of acoustic speech rhythms at frequencies below 10 Hz. Using magnetoencephalography, we compared adults with developmental dyslexia and matched controls while they listened to speech with varying levels of intelligibility (manipulated via noise vocoding). In...
Gahleitner, D.
•
Hauswald, A. K.
•
Weisz, N.
•
Schmidt, F.
bioRxiv
Wed Sep 03 2025
Enriched experience increases reciprocal synaptic connectivity and coding sparsity in higher-order cortex
The integration of new information during sleep reshapes cortical representations that support categorical knowledge. Auto-associative attractor network theories predict that reciprocal excitatory connections help form stable categorical attractors, but direct evidence is missing. We tested this using ten weeks of enriched experience (ENR) in mice as a model for knowledge accumulation and recorded...
Saxena, R.
•
Shobe, J. L.
•
Andujo, A. M.
•
Ning, W.
...•
McNaughton, B. L.
bioRxiv
Wed Sep 03 2025
Stress-Responsive Transcriptomic Signatures in Human iPSC-Derived Microglia Reveal Links to Alzheimer's Disease Risk Genes
Cellular stress responses are essential for maintaining homeostasis in the face of environmental or internal challenges. In the central nervous system, microglia serve as key stress sensors and immune responders, shaping neuroinflammatory processes and disease progression. However, the molecular programs engaged by distinct stressors and their impact on microglial viability remain incompletely und...
Saunders, D.
•
Sultan, F.
•
Vialle, R. A.
•
Kearns, N. A.
...•
Wang, Y.