Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis

Grosse, Ann S.; Pressprich, Mark F.; Curley, Lauren B.; Hamilton, Kara; Margolis, Ben; Hildebrand, Jeffrey D.; Gumucio, Deborah L.

doi:10.1242/jcs.100768

Cited by 30 publications

(52 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S7). Initially, mesenchymal clusters form beneath a highly proliferative pseudostratified epithelium that is uniformly expressing Shh, Ihh, and PdgfA (9,17,43). These initial clusters are regularly spaced, as shown by our pattern analysis, although the mechanisms that determine their initial positioning and even distribution have yet to be elucidated.…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi

Walton

Kolterud

Czerwinski

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

144

230

View full text Add to dashboard Cite

In the adult intestine, an organized array of finger-like projections, called villi, provide an enormous epithelial surface area for absorptive function. Villi first emerge at embryonic day (E) 14.5 from a previously flat luminal surface. Here, we analyze the cell biology of villus formation and examine the role of paracrine epithelial Hedgehog (Hh) signals in this process. We find that, before villus emergence, tight clusters of Hh-responsive mesenchymal cells form just beneath the epithelium. Cluster formation is dynamic; clusters first form dorsally and anteriorly and spread circumferentially and posteriorly. Statistical analysis of cluster distribution reveals a patterned array; with time, new clusters form in spaces between existing clusters, promoting approximately four rounds of villus emergence by E18.5. Cells within mesenchymal clusters express Patched1 and Gli1, as well as Pdgfrα, a receptor previously shown to participate in villus development. BrdU-labeling experiments show that clusters form by migration and aggregation of Hh-responsive cells. Inhibition of Hh signaling prevents cluster formation and villus development, but does not prevent emergence of villi in areas where clusters have already formed. Conversely, increasing Hh signaling increases the size of villus clusters and results in exceptionally wide villi. We conclude that Hh signals dictate the initial aspects of the formation of each villus by controlling mesenchymal cluster aggregation and regulating cluster size.epithelial-mesenchymal cross-talk | field pattern | villus morphogenesis

show abstract

Section: Discussionmentioning

confidence: 67%

“…BrdU (50 mg/kg) was intraperitoneally injected into pregnant females at the stages indicated within the text and prepared as described previously (43).…”

Section: Methodsmentioning

confidence: 99%

Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi

Walton

Kolterud

Czerwinski

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

144

230

View full text Add to dashboard Cite

show abstract

“…The different scales involved, which vary by a factor of 10, show that we must distinguish between the role of mesenchyme from the role of the mucosal epidermis, which is also very active but probably not during the formation of previlli. In addition, for mammalian models such as mice, the structure of the mucosal epidermis, stratified or pseudostratified, has been debated recently (26), bringing a different hypothesis for the growth mechanism itself: addition of layers or intercalation. Focusing on the previlli formation, the folding and zigzag patterns are strongly reminiscent of buckling and secondary instabilities observed in material sciences (27,28), studied theoretically with various elastic models such as Hookean elastic thin sheets (29,30), poroelastic models (31), or finite elasticity for tissue (32)(33)(34).…”

Section: Buckling and Postbuckling Mechanismmentioning

confidence: 99%

Anisotropic growth shapes intestinal tissues during embryogenesis

Amar

Jia

2013

Proc. Natl. Acad. Sci. U.S.A.

139

View full text Add to dashboard Cite

Embryogenesis offers a real laboratory for pattern formation, buckling, and postbuckling induced by growth of soft tissues. Each part of our body is structured in multiple adjacent layers: the skin, the brain, and the interior of organs. Each layer has a complex biological composition presenting different elasticity. Generated during fetal life, these layers will experience growth and remodeling in the early postfertilization stages. Here, we focus on a herringbone pattern occurring in fetal intestinal tissues. Common to many mammalians, this instability is a precursor of the villi, finger-like projections into the lumen. For avians (chicks' and turkeys' embryos), it has been shown that, a few days after fertilization, the mucosal epithelium of the duodenum is smooth, and then folds emerge, which present 2 d later a pronounced zigzag instability. Many debates and biological studies are devoted to this specific morphology, which regulates the cell renewal in the intestine. After reviewing experimental results about duodenum morphogenesis, we show that a model based on simplified hypothesis for the growth of the mesenchyme can explain buckling and postbuckling instabilities. Being completely analytical, it is based on biaxial compressive stresses due to differential growth between layers and it predicts quantitatively the morphological changes. The growth anisotropy increasing with time, the competition between folds and zigzags, is proved to occur as a secondary instability. The model is compared with available experimental data on chick's duodenum and can be applied to other intestinal tissues, the zigzag being a common and spectacular microstructural pattern of intestine embryogenesis.bifurcation | bilayer | neo-Hookean elasticity

show abstract

“…The intestine arises from a specified field of endodermal tissue that is shaped into a tube lined with a rapidly proliferating, pseudostratified epithelium by embryonic day (E) 9.5 in mouse (Grosse et al, 2011;Spence et al, 2011;Wells and Melton, 1999). Over the next 6 days of development, proliferation in the epithelium accompanies a tremendous expansion in the length and circumference of the intestine.…”

Section: Introductionmentioning

confidence: 99%

A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis

et al. 2016

Self Cite

View full text Add to dashboard Cite

During late gestation, villi extend into the intestinal lumen to dramatically increase the surface area of the intestinal epithelium, preparing the gut for the neonatal diet. Incomplete development of the intestine is the most common gastrointestinal complication in neonates, but the causes are unclear. We provide evidence in mice that Yin Yang 1 (Yy1) is crucial for intestinal villus development. YY1 loss in the developing endoderm had no apparent consequences until late gestation, after which the intestine differentiated poorly and exhibited severely stunted villi. Transcriptome analysis revealed that YY1 is required for mitochondrial gene expression, and ultrastructural analysis confirmed compromised mitochondrial integrity in the mutant intestine. We found increased oxidative phosphorylation gene expression at the onset of villus elongation, suggesting that aerobic respiration might function as a regulator of villus growth. Mitochondrial inhibitors blocked villus growth in a fashion similar to Yy1 loss, thus further linking oxidative phosphorylation with late-gestation intestinal development. Interestingly, we find that necrotizing enterocolitis patients also exhibit decreased expression of oxidative phosphorylation genes. Our study highlights the still unappreciated role of metabolic regulation during organogenesis, and suggests that it might contribute to neonatal gastrointestinal disorders.

show abstract

Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis

Cited by 30 publications

References 1 publication

Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi

Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi

Anisotropic growth shapes intestinal tissues during embryogenesis

A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis

Contact Info

Product

Resources

About