Talk:Developmental Mechanism - Tube Formation

From Embryology
About Discussion Pages  
Mark Hill.jpg
On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes:
  1. References - recent and historic that relates to the topic
  2. Additional topic information - currently prepared in draft format
  3. Links - to related webpages
  4. Topic page - an edit history as used on other Wiki sites
  5. Lecture/Practical - student feedback
  6. Student Projects - online project discussions.
Links: Pubmed Most Recent | Reference Tutorial | Journal Searches

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2021, November 30) Embryology Developmental Mechanism - Tube Formation. Retrieved from


Palmer MA & Nelson CM. (2020). Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia. Dev. Dyn. , , . PMID: 32510705 DOI.

Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia

Background: During development of the avian lung, the initially terminally branched epithelial tree later forms a continuous network of airways. This occurs via a large-scale epithelial fusion event, wherein airways that originate proximally collide with those that originate distally to form one continuous lumen.

Results: Here, we found that prior to fusion, the epithelium of the embryonic chicken lung undergoes a shape change to permit the initiation and extension of new branches which contain the cells that initiate contact. These changes in epithelial shape coincide with the differentiation of smooth muscle cells that wrap the airways. From these nascent epithelial branches, individual cells form cytoskeletal protrusions that extend toward and form a bridge with their target airway. Additional cells then join the fusion site, forming a bilayered epithelium. During this process, the basement membrane around the prefusion epithelium degrades and then reforms after fusion. The epithelial bilayer then undergoes apoptosis, clearing the path between the two lumens.

Conclusions: The process of airway epithelial fusion in the developing chicken lung constitutes a novel mechanism for the generation of complex multicellular tubes and suggests a conserved role for smooth muscle in the shaping of airway epithelia.

Keywords: anastomosis; mechanical stress; morphodynamics.


Insane in the apical membrane: Trafficking events mediating apicobasal epithelial polarity during tube morphogenesis

Traffic. 2018 May 16. doi: 10.1111/tra.12579. [Epub ahead of print]

Jewett CE1, Prekeris R1.


The creation of cellular tubes is one of the most vital developmental processes, resulting in the formation of most organ types. Cells have co-opted a number of different mechanisms for tube morphogenesis that vary among tissues and organisms; however, generation and maintenance of cell polarity is fundamental for successful lumenogenesis. Polarized membrane transport has emerged as a key driver not only for establishing individual epithelial cell polarity, but also for coordination of epithelial polarization during apical lumen formation and tissue morphogenesis. In recent years, much work has been dedicated to identifying membrane trafficking regulators required for lumenogenesis. In this review we will summarize the findings from the past couple of decades in defining the molecular machinery governing lumenogenesis both in 3D tissue culture models and during organ development in vivo. KEYWORDS: Rab GTPases; apical lumen formation; endosomes; epithelial polarity; morphogenesis PMID: 29766620 DOI: 10.1111/tra.12579

Network correlation analysis revealed potential new mechanisms for neural tube defects beyond folic acid

Birth Defects Res. 2018 May 6. doi: 10.1002/bdr2.1336. [Epub ahead of print]

Gao X1,2, Finnell RH3,4, Wang H2,5, Zheng Y1,2,5.


BACKGROUND: Neural tube defects (NTDs) are clinically significant congenital malformations which are known to be folic acid (FA) responsive, such that supplementation significantly reduces the prevalence of NTDs. Nonetheless, some individuals fail to respond to FA supplementation; hence NTDs remain a significant public health concern. The mechanisms that underlie the beneficial effects of FA supplementation remain poorly understood. Mouse models have been used extensively to study the mechanisms driving neural tube closure (NTC). METHODS: Microarray data of GSE51285 was downloaded from the NCBI GEO database, which contains the RNA expression profiles of livers from five NTD mouse mutants (heterozygous females) and their corresponding wildtype (WT) controls. Those five NTD mutants have different responsiveness to FA supplementation. The differentially expressed genes (DEGs) between NTD heterozygous and WT mice, as well as the DEGs between FA-responsive and FA-resistant mutants were carefully examined. Weighted gene correlation network analysis (WGCNA) was performed in order to identify genes with high correlations to either FA responsiveness or NTDs, respectively. RESULTS: In total, we identified 18 genes related to the pathogenesis of NTDs, as well as 55 genes related to FA responsiveness. Eight more candidate genes (Abcc3, Gsr, Gclc, Mthfd1, Gart, Bche, Slc25a32, and Slc44a2) were identified by examining the DEGs of those genes involved in the extended folate metabolic pathway between FA-responsive and FA-resistant mutants. CONCLUSIONS: Those genes are involved in mitochondrial choline metabolism, de novo purine synthesis, and glutathione generation, suggesting that formate, choline, and manipulating antioxidant levels may be effective interventions in FA-resistant NTDs. © 2018 Wiley Periodicals, Inc. KEYWORDS: WGCNA; bioinformatics; folic acid; microarray; neural tube defects PMID: 29732722 DOI: 10.1002/bdr2.1336


Effects of nanostructures and mouse embryonic stem cells on in vitro morphogenesis of rat testicular cords

PLoS One. 2013;8(3):e60054. doi: 10.1371/journal.pone.0060054. Epub 2013 Mar 28.

Pan F, Chi L, Schlatt S. Source Institute of Physics, University Münster, Münster, Germany.


Morphogenesis of tubular structures is a common event during embryonic development. The signals providing cells with topographical cues to define a cord axis and to form new compartments surrounded by a basement membrane are poorly understood. Male gonadal differentiation is a late event during organogenesis and continues into postnatal life. The cellular changes resemble the mechanisms during embryonic life leading to tubular structures in other organs. Testicular cord formation is dependent on and first recognized by SRY-dependent aggregation of Sertoli cells leading to the appearance of testis-specific cord-like structures. Here we explored whether testicular cells use topographical cues in the form of nanostructures to direct or stimulate cord formation and whether embryonic stem cells (ES) or soluble factors released from those cells have an impact on this process. Using primary cell cultures of immature rats we first revealed that variable nanogratings exerted effects on peritubular cells and on Sertoli cells (at less than <1000 cells/mm(2)) by aligning the cell bodies towards the direction of the nanogratings. After two weeks of culture testicular cells assembled into a network of cord-like structures. We revealed that Sertoli cells actively migrate towards existing clusters. Contractions of peritubular cells lead to the transformation of isolated clusters into cord-like structures. The addition of mouse ES cells or conditioned medium from ES cells accelerated this process. Our studies show that epithelial (Sertoli cell) and mesenchymal (peritubular cells) cells crosstalk and orchestrate the formation of cords in response to physical features of the underlying matrix as well as secretory factors from ES cells. We consider these data on testicular morphogenesis relevant for the better understanding of mechanisms in cord formation also in other organs which may help to create optimized in vitro tools for artificial organogenesis.

PMID 23555881


MIM regulates vertebrate neural tube closure

Development. 2011 May;138(10):2035-47. Epub 2011 Apr 6.

Liu W, Komiya Y, Mezzacappa C, Khadka DK, Runnels L, Habas R. Source Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.


Neural tube closure is a critical morphogenetic event that is regulated by dynamic changes in cell shape and behavior. Although previous studies have uncovered a central role for the non-canonical Wnt signaling pathway in neural tube closure, the underlying mechanism remains poorly resolved. Here, we show that the missing in metastasis (MIM; Mtss1) protein, previously identified as a Hedgehog response gene and actin and membrane remodeling protein, specifically binds to Daam1 and couples non-canonical Wnt signaling to neural tube closure. MIM binds to a conserved domain within Daam1, and this interaction is positively regulated by Wnt stimulation. Spatial expression of MIM is enriched in the anterior neural plate and neural folds, and depletion of MIM specifically inhibits anterior neural fold closure without affecting convergent extension movements or mesoderm cell fate specification. Particularly, we find that MIM is required for neural fold elevation and apical constriction along with cell polarization and elongation in both the superficial and deep layers of the anterior neural plate. The function of MIM during neural tube closure requires both its membrane-remodeling domain and its actin-binding domain. Finally, we show that the effect of MIM on neural tube closure is not due to modulation of Hedgehog signaling in the Xenopus embryo. Together, our studies define a morphogenetic pathway involving Daam1 and MIM that transduces non-canonical Wnt signaling for the cytoskeletal changes and membrane dynamics required for vertebrate neural tube closure.

PMID 21471152


Kidney development: two tales of tubulogenesis

Curr Top Dev Biol. 2010;90:193-229.

Little M, Georgas K, Pennisi D, Wilkinson L. Source Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia.


The mammalian kidney may well be one of the most complex organs of postnatal life. Each adult human kidney contains on average more than one million functional filtration units, the nephrons, residing within a specialized cellular interstitium. Each kidney also contains over 25 distinct cell types, each of which must be specifically aligned with respect to each other to ensure both normal development and ultimately, normal renal function. Despite this complexity, the development of the kidney can be simplistically described as the coordinate formation of two distinct sets of tubules. These tubules develop cooperatively with each other in time and space, yet represent two distinct but classical types of tubulogenesis. The first of these tubules, the ureteric bud, forms as an outgrowth of another epithelial tube, the nephric duct, and undergoes extensive branching morphogenesis to create the collecting system of the kidney. The second tubules are the nephrons themselves which arise via a mesenchyme-to-epithelial transition induced by the first set of tubules. These tubules never branch, but must elongate to become intricately patterned and functionally segmented tubules. The molecular drivers for these two tales of tubulogenesis include many gene families regulating tubulogenesis and branching morphogenesis in other organs; however, the individual players and codependent interrelationships between a branched and non-branched tubular network make organogenesis in the kidney unique. Here we review both what is known and remains to be understood in kidney tubulogenesis.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID 20691850

Molecular aspects of respiratory and vascular tube development

Respir Physiol Neurobiol. 2010 Aug 31;173 Suppl:S33-6. Epub 2010 Apr 18.

Behr M. Source Life & Medical Sciences Institute, Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31, Bonn, Germany.


Lung, cardiovascular system, liver and kidney are some examples for organs that develop ramified three-dimensional networks of epithelial tubes. The tube morphology affects flow rates of transported materials, such as liquids and gases. Therefore, it is important to understand how tube morphology is controlled. In Drosophila melanogaster many evolutionarily conserved genetic pathways have been shown to be involved in airway patterning. Recent studies identified a number of conserved mechanisms that drive Drosophila airway maturation, such as controlling tube size, barrier formation and lumen clearance. Genetically highly ordered branching modes previously have been found, also for mouse lung development. The understanding of tube patterning, outgrowth, ramification and maturation also is of clinical relevance, since many factors are evolutionarily conserved and may have similar functions in humans. This meeting report highlights novel findings concerning tube development in the fruit fly (D. melanogaster), the zebrafish (Danio rerio) and the laboratory mouse (Mus musculus).

Copyright (c) 2010 Elsevier B.V. All rights reserved.

PMID 20403463

Apical constriction: a cell shape change that can drive morphogenesis

Dev Biol. 2010 May 1;341(1):5-19. Epub 2009 Sep 12. Sawyer JM, Harrell JR, Shemer G, Sullivan-Brown J, Roh-Johnson M, Goldstein B. Source Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.


Biologists have long recognized that dramatic bending of a cell sheet may be driven by even modest shrinking of the apical sides of cells. Cell shape changes and tissue movements like these are at the core of many of the morphogenetic movements that shape animal form during development, driving processes such as gastrulation, tube formation, and neurulation. The mechanisms of such cell shape changes must integrate developmental patterning information in order to spatially and temporally control force production-issues that touch on fundamental aspects of both cell and developmental biology and on birth defects research. How does developmental patterning regulate force-producing mechanisms, and what roles do such mechanisms play in development? Work on apical constriction from multiple systems including Drosophila, Caenorhabditis elegans, sea urchin, Xenopus, chick, and mouse has begun to illuminate these issues. Here, we review this effort to explore the diversity of mechanisms of apical constriction, the diversity of roles that apical constriction plays in development, and the common themes that emerge from comparing systems.

Copyright 2009 Elsevier Inc. All rights reserved.

PMID 19751720