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.

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.

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.

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.

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.

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.

Unbiased intestinal single cell transcriptomics reveals previously uncharacterized enteric nervous system populations in larval zebrafish

The paper performs single-cell RNA sequencing on larval zebrafish ENS to identify previously uncharacterized neuronal and glial populations and reveals a binary neurogenic branching mechanism.

A branching model of cell fate decisions in the enteric nervous system

The paper maps the regulatory landscape of neuronal and glial differentiation in the enteric nervous system using single-cell RNA sequencing and identifies gene modules and epigenetic memory associated with neurogenesis and gliogenesis.

A genetic model of congenital intestinal atresia in medaka (Oryzias latipes) implicates Mypt1 in epithelial organisation

This paper identifies a medaka mutant with congenital intestinal atresia, linking Mypt1 dysfunction to actomyosin dysregulation and epithelial disorganisation.

CHD8-associated gastrointestinal complaints are caused by impaired vagal neural crest development and intestinal homeostatic imbalance

A rapid F0 CRISPR screen in zebrafish to identify regulators of neuronal development in the enteric nervous system

This paper develops a rapid F0 CRISPR screen in zebrafish to identify genes regulating ENS neuronal development and finds five transcription factors that influence ENS neuron differentiation.

Skip segment Hirschsprung disease: modelling the trans-mesenteric origin of the enteric nervous system in the human colon

The paper models trans-mesenteric migration of enteric neural crest cells in humans to explain skip segment Hirschsprung disease.

Whole exome-trio analysis reveals rare variants associated with Congenital Pouch Colon

The paper identifies rare de novo mutations in CPC patients using whole exome sequencing and highlights candidate genes associated with the disorder.

The gastrointestinal development ‘parts list’: transcript profiling of embryonic gut development in wildtype and Ret-deficient mice

The paper profiles RNA-seq data from wildtype and Ret-deficient mouse gut tissues during embryonic development to identify genetic programs involved in enteric nervous system formation and disease.

Epigenetic factors coordinate intestinal development

This paper shows DNA methylation factors are crucial for intestinal development across multiple cell types, including neurons and smooth muscle, and identifies them as potential Hirschsprung disease candidates.