Physical organogenesis of the gut

Abstract

The gut has been a central subject of organogenesis since Caspar Friedrich Wolff’s seminal 1769 work ‘De Formatione Intestinorum’. Today, we are moving from a purely genetic understanding of cell specification to a model in which genetics codes for layers of physical–mechanical and electrical properties that drive organogenesis such that organ function and morphogenesis are deeply intertwined. This Review provides an up-to-date survey of the extrinsic and intrinsic mechanical forces acting on the embryonic vertebrate gut during development and of their role in all aspects of intestinal morphogenesis: enteric nervous system formation, epithelium structuring, muscle orientation and differentiation, anisotropic growth and the development of myogenic and neurogenic motility. I outline numerous implications of this biomechanical perspective in the etiology and treatment of pathologies, such as short bowel syndrome, dysmotility, interstitial cells of Cajal-related disorders and Hirschsprung disease.

In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis

“…5B ). Having established that photopatterning induced curvature results in greater membrane tension, we next investigated the effect of curvature on the resting membrane potential, which is dependent on the membrane tension ( 10 ) and has been highlighted as a possible symmetry breaking cue in homogenous tissues ( 33 ) and as an understudied element of intestinal biomechanics ( 34 ). Using the anionic dye bis-(1,3-diethylthiobarbituric acid) trimethine oxonol (DiSBAC 2 ) ( 3 ), which is concentrated in regions of the lipid bilayer with increasing membrane depolarization, we quantified fluorescence intensity in patterned versus unpatterned regions of the membrane and found significant depolarization in regions of high curvature and tension ( Fig.…”

The IgSF Cell Adhesion Protein CLMP and Congenital Short Bowel Syndrome (CSBS)

“…Several genes have been described in mouse models that interfere with the elongation of the intestine. Most of these genes are linked to the contractility of circular smooth muscle cells [ 58 ]. To better understand the role of CLMP in CSBS, it would be of interest to investigate a link between CLMP and some of these genes.…”

“…Whether the impaired peristalsis observed upon the ablation of Clmp correlates with the process of intestinal elongation in humans is not yet known. It is conceivable that peristalsis is less important for intestinal elongation in mice or the process of elongation, rotation, and herniation might be interrupted or delayed in patients with CSBS [ 58 ].…”

Comprehensive characterization of tumor innervation in colorectal cancer

“…Glial cells surround neurons or axons to provide mechanical protection and nutritional support, playing an undeniable role in maintaining intestinal homeostasis. The ENS is connected to the extrinsic nervous system, forming a large and complex neural network that plays an important role in maintaining the functions and homeostasis of the large intestine [5,8,9].…”