Primary Cilia Regulate Branching Morphogenesis during Mammary Gland Development
Open accessAbstract
During mammary gland development, an epithelial bud undergoes branching morphogenesis to expand into a continuous tree-like network of branched ducts [1]. The process involves multiple cell types that are coordinated by hormones and growth factors coupled with signaling events including Wnt and Hedgehog [2-5]. Primary cilia play key roles in the development of many organs by coordinating extracellular signaling (of Wnt and Hedgehog) with cellular physiology [6-8]. During mammary development, we find cilia on luminal epithelial, myoepithelial, and stromal cells during early branching morphogenesis when epithelial ducts extend into the fat pad and undergo branching morphogenesis. When branching is complete, cilia disappear from luminal epithelial cells but remain on myoepithelial and stromal cells. Ciliary dysfunction caused by intraflagellar transport defects results in branching defects. These include decreased ductal extension and decreased secondary and tertiary branching, along with reduced lobular-alveolar development during pregnancy and lactation. We find increased canonical Wnt and decreased Hedgehog signaling in the mutant glands, which is consistent with the role of cilia in regulating these pathways [6-11]. In mammary gland and other organs, increased canonical Wnt [12-14] and decreased Hedgehog [15, 16] signaling decrease branching morphogenesis, suggesting that Wnt and Hedgehog signaling connect ciliary dysfunction to branching defects.
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Quiescent cells can lose their cilium due to developmental programming or environmental insults such as mechanical stress.
“Quiescent cells can lose their cilium as a consequence of developmental programming 15–19 or in response to environmental insults such as mechanical stress 20.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [16]
The citation to this paper is attached to the claim that mechanical stress can cause quiescent cells to lose their cilium. The Results and Discussion describe reduced cilia in mice with an IFT88 mutation and developmental regression of cilia in rodent ear hair cells, but the passages found by searching for mechanical stress and environmental insults do not address stress-induced cilium loss. (LLM, conf=0.77)
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Cellular signalling by primary cilia in development, organ function and disease
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- Authors
- McDermott, K. M., Liu, B. Y., Tlsty, T. D., & Pazour, G. J.
- Affiliations
- University of Arizona (US)
- University of California, San Francisco (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Tlsty, Thea D.
- Pazour, Gregory J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 20
- Issue
- 8
- Pages
- 731-737
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC2916967
- OpenAlex
- W2018784356
- Cited by
- 100
- References
- 44
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 13
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA097214, CA-58207, R01CA097214, P50CA058207)
- National Institute of General Medical Sciences (GM060992, R01GM060992)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 32520, P30DK032520)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD056965, R00HD056965)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- primary cilia, branching morphogenesis, mammary gland development, Wnt signaling, Hedgehog signaling, intraflagellar transport, myoepithelial cells, luminal cells, stromal cells, lobuloalveolar development, ciliary dysfunction
- MeSH terms
- Animals, Cilia, Female, Mammary Glands, Animal, Mice, Transgenic, Morphogenesis, Pregnancy, Signal Transduction, Wnt Proteins, Mice, Hedgehog Proteins
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