Genetics and Neurodevelopmental Disorders

Astrocytic Regulation of aberrant perineuronal net formation in Mecp2-null Neocortex

This study identifies Mecp2-null astrocytes as drivers of precocious perineuronal net formation in RTT by inducing Hapln1 expression and accelerating PNN maturation.

CDKL5 phosphorylates neuronal ELAVL proteins to promote mRNA binding, protein synthesis and visual cortex development

This study identifies CDKL5 as a kinase that phosphorylates nELAVL proteins, enhancing mRNA binding and protein synthesis, and shows its role in visual cortex development.

Cortical Organoid Model of PPP2R5D Genetic Intellectual Disability Models Disease Severity Phenotype

This study uses cortical organoids to model PPP2R5D mutations in Jordans Syndrome, identifying gene expression, protein, and electrophysiological changes linked to disease severity.

MeCP2 is Necessary in Cerebellar Purkinje Cells for Precise Network Dynamics During Associative Motor Learning

This study shows that MeCP2 in Purkinje cells is critical for precise timing and coordination in cerebellar learning but not for general motor behaviors.

Intersection of Regulatory Analysis and Signature Reversion Uncovers Therapeutic Drugs and Targets for SETBP1-HD

The paper identifies therapeutic drugs and targets for SETBP1-HD by integrating regulatory analysis and signature reversion across transcriptomic datasets.

CDKL5 deficiency results in atypical subregion-specific expression of perineuronal nets during mouse visual critical period

This study examines PNN expression in the V1 of CDKL5-deficient mice during the visual critical period, finding increased and subregion-specific PNN expression compared to controls.

Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of Fragile X mice and identifies EPAC2 as a therapeutic target.

Early and transient increase in cortical pyramidal cell excitability and delayed alteration of evoked synaptic transmission and t-SNARE proteins content in the hippocampus and neocortex of neonatal and juvenile STXBP1 heterozygous mice

This study examines the developmental stage-dependent effects of Munc18.1 deficiency on neuronal excitability and synaptic transmission in STXBP1 heterozygous mice.

Dysfunction of a SET3-like complex underlies a family of related neurological disorders

The paper identifies a dysfunction in the SET3-like complex involving TBLR1, ANKRD11, and SETD5 as a molecular basis for neurodevelopmental disorders.

A novel mouse model of rare neurodevelopmental disorder, TBCK Syndrome

This study creates a mouse model of TBCK Syndrome by knocking out the Tbck gene, revealing early neurodevelopmental phenotypes and systemic alterations consistent with the human disorder.

Transcriptomic-guided compound prioritization and proteomics validation for HNRNPU deficiency identify signalling correction

The paper develops a transcriptomic-guided compound prioritization pipeline and validates it with proteomics, identifying two compounds that partially rescue HNRNPU deficiency phenotypes.

NeuroDev: etiology and experience of neurodevelopmental disorders in Kenya and South Africa

The paper presents genetic and phenotypic data from 521 children with neurodevelopmental disorders in Kenya and South Africa, highlighting high genetic diagnosis rates linked to environmental risk factors.

A genetic screen reveals dosage-sensitive effects of ASD genes and identifies domino as a regulator of synaptic and behavioral phenotypes

Exaggerated NMDA Receptor-Primed Metaplasticity via SK Channel Dysregulation in Fmr1 Knockout Mice

This study shows that Fmr1 knockout mice exhibit exaggerated NMDA receptor-mediated metaplasticity due to SK channel dysregulation, affecting hippocampal LTP and potentially contributing to learning impairments in Fragile X syndrome.

Chromosome 2q31.2 Deletion Impairs Neuronal Plasticity through Integrated Stress Response Activation

This study investigates how a chromosome 2q31.2 deletion affects neuronal plasticity by activating the integrated stress response (ISR) and shows that ISR inhibition improves neuronal function.

MECP2 Mutations Rewire Human ESC Fate and Bias Cortical Lineage Commitment

This study shows MECP2 mutations alter human ESC fate and bias cortical lineage commitment by affecting ZFP42 and EMX1 expression.

Suppression of astrocyte BMP signaling improves fragile X syndrome molecular signatures and functional deficits

This study shows suppressing BMP signaling in astrocytes reduces molecular and functional deficits in fragile X syndrome.

Preclinical evaluation of antisense oligonucleotide therapy in a mouse model of HNRNPH2-related neurodevelopmental disorder

This study tests antisense oligonucleotides targeting Hnrnph2 in a mouse model, showing reduced Hnrnph2 levels, increased Hnrnph1, and improved phenotypes like seizures and motor function.

Female cortical cellular mosaicism underlies shared MeCP2 and PCB impacted gene pathways

The paper investigates how PCB exposure interacts with MeCP2 mutations in female mice, identifying shared gene pathways and transcriptional impacts in the cortex.

Mecp2 deficiency induces dysphagia in a preclinical model of Rett Syndrome

This study investigates how Mecp2 deficiency affects swallow-related neuromuscular mechanisms in Rett Syndrome, finding impaired cholinergic signaling and submental muscle activity in Mecp2-deficient mice.

Reduced cortico-accumbal excitatory input due to Nav1.2 haploinsufficiency impairs sociability independently of dopamine

This study shows that reduced excitatory input to the nucleus accumbens due to Scn2a haploinsufficiency impairs sociability without affecting dopamine levels.

Reversing Pathophysiology in Fragile X Syndrome Mice by Promoting PGC-1α and Mitochondrial Functions

This study shows that promoting PGC-1α and mitochondrial functions in FXS mice improves cognition and reduces autism-like behaviors.

Diminished signal-to-noise ratio disrupts somatosensory population encoding and drives tactile hyposensitivity in the Fmr1-/y autism model.

The paper shows that reduced signal-to-noise ratio in neurons impairs tactile perception in an autism mouse model, leading to hyposensitivity.

Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cerebral organoids

This study examines how different MeCP2 mutations affect neuronal activity and network function in Rett syndrome organoids, finding mutation-specific impairments in connectivity and gene expression.

Concordant transcriptional and morphological remodeling revealed by in vivo Perturb-CLEAR

The paper develops Perturb-CLEAR to study dendritic morphogenesis in the developing mouse cortex, revealing gene-specific multimodal phenotypes linked to NDD risk genes.

Neuronal differentiation and activity drive nucleocytoplasmic shuttling of the intellectual disability kinase TLK2

The paper investigates the expression and subcellular localization of TLK2 in neurons, showing that neuronal differentiation and activity drive its nucleocytoplasmic shuttling.

Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.

This study shows that reducing leptin signaling alleviates Rett syndrome symptoms in Mecp2-deficient mice by improving neurological and physiological functions.

Deficits in forelimb reach learning in a mouse model of Fragile X syndrome

This study investigates motor learning deficits in Fmr1 KO mice, showing that reward cues alleviate some impairments and identifying specific behavioral parameters linked to learning success.

Spatially resolved mapping of histones reveal selective neuronal response in Rett syndrome

This study uses mass spectrometry imaging and laser capture microdissection to analyze histone proteoforms in RTT mouse models, revealing neuron-specific differences and mutation-dependent chromatin changes.

Selective Shank3 Deletion in Glutamatergic Neurons of the Anterior Insular Cortex Induces Autism-Related Behavior and Circuit Dysfunction

This study shows that deleting Shank3 in glutamatergic neurons of the anterior insular cortex causes autism-like behaviors and circuit dysfunction in mice.