Villus myofibroblasts are developmental and adult progenitors of mammalian gut lymphatic musculature.

Inside the finger-like intestinal projections called villi, strands of smooth muscle cells contract to propel absorbed dietary fats through the adjacent lymphatic capillary, the lacteal, sending fats into the systemic blood circulation for energy production. Despite this vital function, mechanisms of formation, assembly alongside lacteals, and maintenance of villus smooth muscle are unknown. By combining single-cell RNA sequencing and quantitative lineage tracing of the mouse intestine, we identified a local hierarchy of subepithelial fibroblast progenitors that differentiate into mature smooth muscle fibers via intermediate contractile myofibroblasts.

Origin and adult renewal of the gut lacteal musculature from villus myofibroblasts.

Intestinal smooth muscles are the workhorse of the digestive system. Inside the millions of finger-like intestinal projections called villi, strands of smooth muscle cells contract to propel absorbed dietary fats through the adjacent lymphatic vessel, called the lacteal, sending fats into the blood circulation for energy production. Despite this vital function, how villus smooth muscles form, how they assemble alongside lacteals, and how they repair throughout life remain unknown.

patterns an accelerator-brake mechanical feedback through latent TGFβ to rotate the gut.

The vertebrate intestine forms by asymmetric gut rotation and elongation, and errors cause lethal obstructions in human infants. Rotation begins with tissue deformation of the dorsal mesentery, which is dependent on left-sided expression of the Paired-like transcription factor . The conserved morphogen induces asymmetric to govern embryonic laterality, but organ-level regulation of during gut asymmetry remains unknown.

Protocol to detect smooth muscle actin-alpha and measure oxidative damage in neonatal mouse intestine.

This protocol describes how to characterize α-Smooth muscle actin (αSMA) spatiotemporal expression during mouse small intestinal development. Specific tissue fixation preserves αSMA arrangement in low αSMA expressing cells that are conventionally undetectable under αSMA immunofluorescent stain due to inappropriate fixative-caused artificial actin depolymerization. Parallel analysis of αSMA carbonylation allows estimation of oxidative damage in gut muscular lineage.

The asymmetric Pitx2 gene regulates gut muscular-lacteal development and protects against fatty liver disease.

Intestinal lacteals are essential lymphatic channels for absorption and transport of dietary lipids and drive the pathogenesis of debilitating metabolic diseases. However, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover an intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2.

Coronary Arteries Shake Up Developmental Dogma.

The leading cause of death worldwide is disease of the coronary arteries, the vessels that nourish the heart muscle. However, mechanisms that control their development and possible regeneration remain unknown. Recent work is challenging current dogma of coronary artery origins and illuminating key programs that govern coronary artery formation.

Two Zebrafish hsd3b Genes Are Distinct in Function, Expression, and Evolution.

HSD3B catalyzes the synthesis of δ4 steroids such as progesterone in the adrenals and gonads. Individuals lacking HSD3B2 activity experience congenital adrenal hyperplasia with imbalanced steroid synthesis. To develop a zebrafish model of HSD3B deficiency, we characterized 2 zebrafish hsd3b genes.

Ethanol inhibits retinal and CNS differentiation due to failure of cell cycle exit via an apoptosis-independent pathway.

Alcohol exposure during embryogenesis results in a variety of developmental disorders. Here, we demonstrate that continuous exposure to 1.5% ethanol causes substantial apoptosis and abrogated retinal and CNS development in zebrafish embryos.