Congenital gastrointestinal and neural anomalies

Notch signalling governs human enteric nervous system progenitor dynamics

This study shows Notch signalling regulates human ENS progenitor dynamics, affecting differentiation and migration, and links its disruption to intestinal aganglionosis.

GDNF enemas improve epithelial and immune defects in both aganglionic and ganglionic colon of Hirschsprung mice

This study shows that GDNF enemas improve epithelial and immune defects in both aganglionic and ganglionic colon of Hirschsprung mice, reducing bacterial translocation and inflammation.

Trisomy 21 Impairs Development of Enteric Neural Crest-Derived Cells via SOD1-Mediated RET Dysregulation

This study shows Trisomy 21 impairs enteric neural crest development by reducing RET expression through SOD1-mediated oxidative stress.

Validation of the VACTERL Episignature and Evidence for Epigenomic Convergence Across Recurrent Constellations of Embryonic Malformations

The paper validates a DNA methylation episignature for VACTERL and finds evidence of epigenomic convergence across related embryonic malformation conditions.

BxbI-mediated insertion of a 77kb human RET sensitive haplotype into the mouse genome to generate a humanized model of Hirschsprung disease

This study inserts a human RET haplotype into mice to model Hirschsprung disease, finding that regulatory variants reduce RET expression and contribute to disease.

Abnormal enteric nervous system organization and gastrointestinal motility in mice with valproic acid-induced neural tube defects

A neuroimmune IL-13 axis is associated with human enteric nervous system development

This study identifies a neuroimmune IL-13 axis involved in human enteric nervous system development through transcriptomic and functional analyses of neonatal ileum tissue.

ENS lineage potential is not intrinsically regionalized but is modulated by PTPRZ1 signaling

The paper shows the enteric nervous system (ENS) lacks intrinsic regionalization but is shaped by PTPRZ1 signaling from the gut microenvironment during development.

Sod1 trisomy causes ENS developmental defects and susceptibility to Hirschsprung disease via neuronal Ret suppression and glial remodeling

This study shows that SOD1 trisomy disrupts ENS development and increases HSCR risk by reducing RET expression and altering glial states.

Endothelin 3 and T-type Ca2+ channels drive enteric neural crest cell calcium activity, contractility and migration

This study shows that endothelin 3 and T-type Ca2+ channels regulate calcium activity, contractility, and migration of enteric neural crest cells, linking these processes to Hirschsprung disease.

Combinatorial multiomic analysis from a pedigree of Sox10Dom Hirschsprung mice implicates Dach1 as a modifier of Enteric Nervous System development

The paper identifies genetic modifiers of Hirschsprung disease severity using a mouse model and multiomic analysis of the Enteric Nervous System.

Functional and molecular rescue of aganglionic colon by human enteric nervous system progenitor transplantation in Hirschsprung disease

This study demonstrates that transplanting human pluripotent stem cell-derived enteric nervous system progenitors can improve contractile function and rescue molecular pathways in Hirschsprung disease colonic tissue.

PHOX2B polyalanine repeat mutation has a profound impact on the transcriptome of neuronal progenitor cells in Haddad syndrome

This study uses RNA-sequencing to show that PHOX2B polyalanine repeat mutation significantly alters the transcriptome of neuronal progenitor cells in Haddad syndrome.

A call for a unified and multimodal definition of cellular identity in the enteric nervous system

The paper highlights the need for a unified multimodal approach to define cellular identity in the enteric nervous system using transcriptomic and other omics data.

Whole-gut spatial genomic analysis reveals molecular regionalization of the differentiating zebrafish enteric nervous system

This study uses whole-gut spatial genomic analysis in zebrafish to identify regionalized gene expression patterns in the developing enteric nervous system.

Single-cell RNA sequencing in Hirschsprungs disease tissues reveals lack of neuronal differentiation in the aganglionic colon segment

This study uses scRNA-seq and WGS to analyze HSCR patient tissues, identifying impaired neuronal differentiation in aganglionic colon segments.

The metabolic kinase LKB1 shapes the enteric nervous system bymitigating the oxidative stress and p53 activity

This paper shows that LKB1 is essential for ENS development by reducing oxidative stress and p53 activity, leading to hypoganglionosis and digestive issues when LKB1 is lost.

GDNF regenerates the missing enteric nervous system of Hirschsprung mice via non-canonical signaling in diverse subtypes of tissue-resident progenitors

This study shows GDNF regenerates the missing enteric nervous system in Hirschsprung mice through non-canonical signaling in tissue-resident progenitors, suggesting potential for broader therapeutic applications.

Joint disruption of Ret and Ednrb transcription drives cell fate reversal in the Enteric Nervous System in Hirschsprung disease

This study shows that reduced function alleles in Ret and Ednrb genes cause Hirschsprung disease by disrupting their gene regulatory network and leading to cell fate reversal in the enteric nervous system.

Variability in proliferative and migratory defects in Hirschsprung disease-associated RET pathogenic variants

The paper assesses the functional impact of RET pathogenic variants in Hirschsprung disease by analyzing their effects on cell proliferation and migration in a neural crest-derived cell line.

Dietary manipulation of intestinal microbes prolongs survival in a mouse model of Hirschsprung disease

This study shows that diet can significantly affect survival in a mouse model of Hirschsprung disease by altering gut microbes, metabolites, and epithelial gene expression.

Rdh10-mediated Retinoic Acid Signaling Regulates the Neural Crest Cell Microenvironment During ENS Formation

This study identifies Rdh10 as a key regulator of retinoic acid signaling that controls neural crest cell migration during enteric nervous system formation, leading to intestinal aganglionosis in its absence.

Combined effects of Ret coding and enhancer loss-of-function alleles cause progressive loss of inhibitory motor neurons in the enteric nervous system

The paper investigates how a non-coding variant in a RET enhancer and a coding null allele together cause loss of inhibitory motor neurons in the enteric nervous system, leading to Hirschsprung disease.

The Role of de novo and Ultra-Rare Variants in Hirschsprung Disease (HSCR): Extended Gene Discovery for Risk Profiling of Patients

The paper identifies 19 risk genes for Hirschsprung Disease, including 15 novel candidates, showing ultra-rare variants contribute significantly to disease risk and severity.

Structure-based mechanistic principles underlying the paradoxical effects of pathological RET mutations

This study identifies structural mechanisms explaining how certain RET mutations cause both Hirschsprungs disease and MEN2A by disrupting protein structure and promoting dimerization.

Lineage-specific intersection of endothelin and GDNF signaling in enteric nervous system development

The paper shows that two distinct ENS progenitor lineages use endothelin signaling differently to support migration to the hindgut.

Single Cell Profiling in the Sox10Dom/+ Hirschsprung Mouse Implicates Hoxa6 in Enteric Neuron Lineage Allocation

The paper uses scRNA-seq to study Sox10 deficiency in mice, finding Hoxa6 is involved in enteric neuron lineage allocation.

A targeted CRISPR-Cas9 mediated F0 screen identifies genes involved in establishment of the enteric nervous system

This study uses a CRISPR-Cas9 screen in zebrafish to identify genes involved in enteric nervous system development, revealing opioid receptor involvement in ENS establishment.

RET enhancer haplotype-dependent remodeling of the human fetal gut development program

The paper shows RET enhancer variants reduce gene expression and alter the fetal gut development program, potentially causing Hirschsprung disease through effects on neural crest cell proliferation.

Ret loss-of-function decreases enteric neural crest progenitor proliferation and restricts developmental fate potential during enteric nervous system development

This study shows that Ret loss-of-function in mouse embryos reduces enteric neural crest progenitor proliferation and limits neuronal fate potential during ENS development.