Evidence map›Paper›PMID 33705716›Full record

ArticleCurrent biology : CB2021

Local accumulation of extracellular matrix regulates global morphogenetic patterning in the developing mammary gland.

Bryan A Nerger, Jacob M Jaslove, Hader E Elashal, Sheng Mao, Andrej Košmrlj, A James Link, Celeste M Nelson

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Extracellular Matrix Viscoelasticity Regulates Mammary Branching Morphogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Basement membrane patterning by spatial deployment of a secretion-regulating protease.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. The Mechanics of Building Functional Organs.Cold Spring Harbor perspectives in biology · 2025
    Review
  12. Embryonic Mammary Gland Morphogenesis.Advances in experimental medicine and biology · 2025
    Review
  13. Review
  14. Article
  15. Mechanisms of assembly and remodelling of the extracellular matrix.Nature reviews. Molecular cell biology · 2024
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Bryan A NergerDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Jacob M JasloveDepartment of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Graduate School of Biomedical Sciences, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Hader E ElashalDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Sheng MaoDepartment of Mechanics and Engineering Science, BIC-ESAT, College of Engineering, Peking University, Beijing 100871, China; Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544, USA.
Andrej KošmrljDepartment of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544, USA.
A James LinkDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Celeste M NelsonDepartment of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: celesten@princeton.edu.
Princeton University · USEnvironmental and Occupational Health Sciences Institute · US

Funding

Lasso Peptide DiscoveryR01GM107036 · NIGMS · PRINCETON UNIVERSITY · PI LINK, AARON JAMES · 2014 to 2022
$2.9M
Biophysical and Biochemical Effects of the ECM on Breast Epithelial CellsR01CA187692 · NCI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M, RADISKY, DEREK C · 2015 to 2019
$2.1M
Mechanical Regulation of Mesenchyme and Mammalian Lung DevelopmentR01HL120142 · NHLBI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M · 2014 to 2017
$1.6M
Exogenous Fluid Forces and Branching of the Mammalian LungR21HL118532 · NHLBI · PRINCETON UNIVERSITY · PI NELSON, CELESTE M · 2014 to 2015
$442k
Mechanical Control of Smooth Muscle Differentiation During Mouse Lung BranchingF30HL139039 · NHLBI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI JASLOVE, JACOB MICHAEL · 2017 to 2022
$296k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA187692NHLBI NIH HHS F30 HL139039NHLBI NIH HHS R01 HL120142NHLBI NIH HHS R21 HL118532NIGMS NIH HHS R01 GM107036
6 · The paper itself

Abstract

The tree-like pattern of the mammary epithelium is formed during puberty through a process known as branching morphogenesis. Although mammary epithelial branching is stochastic and generates an epithelial tree with a random pattern of branches, the global orientation of the developing epithelium is predictably biased along the long axis of the gland. Here, we combine analysis of pubertal mouse mammary glands, a three-dimensional (3D)-printed engineered tissue model, and computational models of morphogenesis to investigate the origin and the dynamics of the global bias in epithelial orientation during pubertal mammary development. Confocal microscopy analysis revealed that a global bias emerges in the absence of pre-aligned networks of type I collagen in the fat pad and is maintained throughout pubertal development until the widespread formation of lateral branches. Using branching and annihilating random walk simulations, we found that the angle of bifurcation of terminal end buds (TEBs) dictates both the dynamics and the extent of the global bias in epithelial orientation. Our experimental and computational data demonstrate that a local increase in stiffness from the accumulation of extracellular matrix, which constrains the angle of bifurcation of TEBs, is sufficient to pattern the global orientation of the developing mammary epithelium. These data reveal that local mechanical properties regulate the global pattern of mammary epithelial branching and may provide new insight into the global patterning of other branched epithelia.

Indexed as

Extracellular MatrixMammary Glands, AnimalAnimalsEpitheliumMiceMorphogenesisbiofabricationcollective migrationfinite element methodmechanical stressmechanotransductionmorphodynamicstissue engineering

Identifiers

PMID33705716
PMCPMC8119325
OpenAlexW3133599942

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.