Patterning and folding of intestinal villi by active mesenchymal dewetting.
Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with in vitro and in vivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film.
Pubmed ID: 38781967 RIS Download
Research resources used in this publication
- Myh10tm7Rsad/Myh10tm7Rsad (RRID:MGI:4443040) (organism)
- Myh9tm5Rsad/Myh9tm5Rsad (RRID:MGI:4838530) (organism)
- B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J (RRID:IMSR_JAX:007914) (organism)
- B6.129S-Pdgfratm1.1(cre/ERT2)Blh/J (RRID:IMSR_JAX:032770) (organism)
- STOCK Gt(ROSA)26Sortm1(CAG-Brainbow2.1)Cle/J (RRID:IMSR_JAX:013731) (organism)
- B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (RRID:IMSR_JAX:007676) (organism)
- B6.129X1-Twist2tm1.1(cre)Dor/J (RRID:IMSR_JAX:008712) (organism)
- B6.129S6-Shhtm2(cre/ERT2)Cjt/J (RRID:IMSR_JAX:005623) (organism)
- B6.129S4-Pdgfratm11(EGFP)Sor/J (RRID:IMSR_JAX:007669) (organism)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- α-Smooth Muscle Actin (1A4) Mouse mAb (IHC Formulated) (RRID:AB_2799522)
- COLLAGEN Type I Antibody (RRID:AB_2074625)
- Anti-phospho-Histone H3 (Ser10) Antibody (RRID:AB_310177)
- CDH11 Polyclonal Antibody (RRID:AB_2533995)
- Mouse Cadherin-4/R-Cadherin Affinity Purified Polyclonal Ab (RRID:AB_10890570)
- RABBIT ANTI MOUSE COLLAGEN IV (RRID:AB_2082660)
- Fibronectin antibody (RRID:AB_2262874)
- Anti-Myosin Light Chain Kinase antibody, Mouse monoclonal (RRID:AB_3076644)
- Rabbit Anti-Myosin, light chain, phospho (Ser20) Polyclonal Antibody, Unconjugated (RRID:AB_303094)
- Myosin IIc (D4A7) Rabbit mAb (RRID:AB_10886923)
- Purified Non-muscle Myosin Heavy Chain II-B (RRID:AB_2749903)
- Purified Non-muscle Myosin Heavy Chain II-A (RRID:AB_2734686)
- Goat Anti-Human Pdgf r alpha Polyclonal antibody, Unconjugated (RRID:AB_354459)
- Mouse PDGF R alpha Antibody (RRID:AB_2236897)
- Purified Mouse Anti-E-cadherin (RRID:AB_397580)
- E-Cadherin (24E10) Rabbit mAb (RRID:AB_2291471)
Associated grants
- Agency: NIDCR NIH HHS, United States
Id: R35 DE026602 - Agency: NIDDK NIH HHS, United States
Id: F32 DK128949 - Agency: NCI NIH HHS, United States
Id: U01 CA244109 - Agency: NIDDK NIH HHS, United States
Id: R01 DK126376 - Agency: NIGMS NIH HHS, United States
Id: R01 GM135462 - Agency: NCI NIH HHS, United States
Id: R33 CA247744 - Agency: NIDDK NIH HHS, United States
Id: U01 DK103147
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This is a list of tools and resources that we have found mentioned in this publication.
α-Smooth Muscle Actin (1A4) Mouse mAb (IHC Formulated) (antibody)
RRID:AB_2799522
This monoclonal targets ACTA2
View all literature mentionsCOLLAGEN Type I Antibody (antibody)
RRID:AB_2074625
This polyclonal targets COLLAGEN Type I
View all literature mentionsAnti-phospho-Histone H3 (Ser10) Antibody (antibody)
RRID:AB_310177
This unknown targets phospho-Histone H3 (Ser10)
View all literature mentionsCDH11 Polyclonal Antibody (antibody)
RRID:AB_2533995
This unknown targets CDH11
View all literature mentionsMouse Cadherin-4/R-Cadherin Affinity Purified Polyclonal Ab (antibody)
RRID:AB_10890570
This unknown targets Mouse Cadherin-4/R-Cadherin Affinity Purified Ab
View all literature mentionsRABBIT ANTI MOUSE COLLAGEN IV (antibody)
RRID:AB_2082660
This polyclonal targets Col4a3
View all literature mentionsFibronectin antibody (antibody)
RRID:AB_2262874
This polyclonal targets Fibronectin
View all literature mentionsAnti-Myosin Light Chain Kinase antibody, Mouse monoclonal (antibody)
RRID:AB_3076644
This monoclonal targets Myosin Light Chain Kinase
View all literature mentionsRabbit Anti-Myosin, light chain, phospho (Ser20) Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_303094
This polyclonal targets Myosin light chain (phospho S20)
View all literature mentionsMyosin IIc (D4A7) Rabbit mAb (antibody)
RRID:AB_10886923
This monoclonal targets Myosin IIc (D4A7) Rabbit mAb
View all literature mentionsPurified Non-muscle Myosin Heavy Chain II-B (antibody)
RRID:AB_2749903
This unknown targets Myosin-10
View all literature mentionsPurified Non-muscle Myosin Heavy Chain II-A (antibody)
RRID:AB_2734686
This unknown targets Myosin-9
View all literature mentionsGoat Anti-Human Pdgf r alpha Polyclonal antibody, Unconjugated (antibody)
RRID:AB_354459
This polyclonal targets Human PDGF R alpha
View all literature mentionsMouse PDGF R alpha Antibody (antibody)
RRID:AB_2236897
This polyclonal targets Mouse PDGF R alpha
View all literature mentionsPurified Mouse Anti-E-cadherin (antibody)
RRID:AB_397580
This monoclonal targets E-cadherin
View all literature mentionsE-Cadherin (24E10) Rabbit mAb (antibody)
RRID:AB_2291471
This monoclonal targets E-Cadherin (24E10) Rabbit mAb
View all literature mentionsMyh10tm7Rsad/Myh10tm7Rsad (organism)
RRID:MGI:4443040
Allele Detail: Targeted This is a legacy resource.
View all literature mentionsMyh9tm5Rsad/Myh9tm5Rsad (organism)
RRID:MGI:4838530
Allele Detail: Targeted This is a legacy resource.
View all literature mentionsB6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J (organism)
RRID:IMSR_JAX:007914
Mus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsB6.129S-Pdgfratm1.1(cre/ERT2)Blh/J (organism)
RRID:IMSR_JAX:032770
Mus musculus with name B6.129S-Pdgfratm1.1(cre/ERT2)Blh/J from IMSR.
View all literature mentionsSTOCK Gt(ROSA)26Sortm1(CAG-Brainbow2.1)Cle/J (organism)
RRID:IMSR_JAX:013731
Mus musculus with name STOCK Gt(ROSA)26Sortm1(CAG-Brainbow2.1)Cle/J from IMSR.
View all literature mentionsB6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (organism)
RRID:IMSR_JAX:007676
Mus musculus with name B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.
View all literature mentionsB6.129X1-Twist2tm1.1(cre)Dor/J (organism)
RRID:IMSR_JAX:008712
Mus musculus with name B6.129X1-Twist2tm1.1(cre)Dor/J from IMSR.
View all literature mentionsB6.129S6-Shhtm2(cre/ERT2)Cjt/J (organism)
RRID:IMSR_JAX:005623
Mus musculus with name B6.129S6-Shhtm2(cre/ERT2)Cjt/J from IMSR.
View all literature mentionsB6.129S4-Pdgfratm11(EGFP)Sor/J (organism)
RRID:IMSR_JAX:007669
Mus musculus with name B6.129S4-Pdgfratm11(EGFP)Sor/J from IMSR.
View all literature mentions
