December 18, 2014

You might not want the dreaded tube socks in your Christmas stocking this year, but you do appreciate the actual tubes that your body depends on in just about every organ system. A recent paper in PLOS Biology describes tube formation in the fly renal system and the signals that regulate it.

Tubes generally start as buds that dramatically elongate during development, but the cell rearrangements that occur during tubulogenesis are not completely understood. Saxena and colleagues recently used the developing fly renal system to track cell movements during tube formation. Tubule elongation primarily occurs through convergent extension, during which cells intercalate along the length of the tube. During these rearrangements, the number of cells around the circumference of the tube drops as the number of cells along the tube increases. Saxena and colleagues show that epidermal growth factor localized at the tip cells of the distal end of the tube guides the polarity of cell rearrangements, via polarization of Myosin II within individual cells. Finally, without proper tube elongation, animals have abnormal excretory function and osmoregulation, leading to lethality. In the images above, the top row shows failure of tube elongation after laser ablation of the distal tip cells (arrowheads). Bottom row shows normal tube elongation without laser ablation of tip cells (arrowheads).

Saxena, A., Denholm, B., Bunt, S., Bischoff, M., VijayRaghavan, K., & Skaer, H. (2014). Epidermal Growth Factor Signalling Controls Myosin II Planar Polarity to Orchestrate Convergent Extension Movements during Drosophila Tubulogenesis PLoS Biology, 12 (12) DOI: 10.1371/journal.pbio.1002013

August 19, 2014

Think of life without tubes for a moment. Not only would our huge bodies cease to exist, but our homes’ plumbing would be a mess and my 5-year old’s marble run would be pretty boring. The formation of tubes during development is a fascinating topic. Today’s image is from a paper describing the role of endocytosis in seamless tube formation.

The trachea of the fruit fly is a simple tubular system that functions as the respiratory system of the fly. The star-shaped tracheal terminal cells form seamless tubes that extend the length of long cellular extensions. Schottenfeld-Roames and colleagues recently published a study investigating the mutations in the braided gene. Tracheal terminal cells in braided mutants have tubular cysts and fewer branches, as seen in the images above (top is wild-type; bottom is mutant). braided encodes Syntaxin7, a endocytosis protein that promotes fusion of vesicles to early endosomes. Schottenfeld-Roames and colleagues found that mutations in other early endosome proteins cause similar terminal cell tube defects. Additional data showing increased levels of the apical protein Crumbs in braided terminal cells suggests that early endocytosis regulates levels of Crumbs, which in turn affects tube formation through actin cytoskeleton modulation. The images above show the luminal membrane (green) and an apical protein (magenta) in tracheal tubes. The tubes in braided mutants are cystic and abnormal, and the tube tips are disorganized (higher magnified views of the boxed regions are on the left).

Schottenfeld-Roames, J., Rosa, J., & Ghabrial, A. (2014). Seamless Tube Shape Is Constrained by Endocytosis-Dependent Regulation of Active Moesin Current Biology, 24 (15), 1756-1764 DOI: 10.1016/j.cub.2014.06.029
Copyright ©2014 Elsevier Ltd. All rights reserved.

All the images were acquired by Dr. Jodi Schottenfeld-Roames.

August 6, 2012

Morphogenesis may be a big word, but the concept is simple and beautiful. Morphogenesis refers to how cells become shaped and organized into complete tissue or organs….and eventually an actual organism. Morphogenesis is what countless developmental biologists think about as they fall asleep, as they wake up, as they shower…how about that for obsession?! Today’s image is from a paper on epithelial morphogenesis—specifically the formation of tube structures in a liver.

Understanding how cells rearrange themselves into tissue structures is a main goal of developmental biology. Many structures rely on epithelial cells that line a lumen. For example, the tubular bile ducts of the liver are made of epithelial cells that both regulate the composition of bile and prevent leakage of bile along the tube. These epithelial cells are called cholangiocytes, and a recent paper paves the way towards understanding how these cells form the tube structures during development. In this paper, Senga and colleagues identified a transcription factor called grainyhead-like 2 (Grhl2) that regulates the size of a lumen surrounded by epithelial cells during development. Grhl2 upregulates claudin 3 and claudin 4, components of the tight junctions that provide a tight barrier between epithelial cells. Grhl2 also targets Rab25, which in turn increases claudin 4 levels and regulates its localization at tight junctions. As seen in the images above, expression of Grhl2 (bottom row) in cysts of liver progenitor cells causes rapid expansion of the lumen inside of the cysts without increasing the number of cells, compared with the slow formation of the lumen in a control cyst (top row).

Kazunori Senga, Keith E. Mostov, Toshihiro Mitaka, Atsushi Miyajima, & Naoki Tanimizu (2012). Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25 Molecular Biology of the Cell, 23 (15), 2845-2855 DOI: 10.1091/mbc.E12-02-0097

September 5, 2011

When you hear the word “angiogenesis,” do you start hissing? Many of us associate angiogenesis with tumors on their way to becoming malignant cancer. Well, if it weren’t for angiogenesis, we’d all be in trouble. Angiogenesis is the formation of blood vessels from pre-existing ones, and is a key process during development.

Blood vessels are the tubular structures that transport all of the good stuff in our blood. The formation of blood vessels depends on angiogenesis, the process in which vessels are created from pre-existing ones. Angiogenesis is a tightly regulated process, as the blood vessels in many organs have a stereotypic organization, abundance, and shape. For example, zebrafish embryos have a regular pattern of blood vessels sprouting from the aorta, along the trunk of the fish. A recent paper describes the importance of Semaphorin-PlexinD1 signaling in the organization of these blood vessels. According to Zygmunt and colleagues, Semaphorin-PlexinD1 signaling ensures the correct spatial distribution and number of blood vessels along the embryo’s trunk. Without correct Semaphorin-PlexinD1 signaling, too many vessels sprout along the aorta, as seen in the images above. Normal embryos (left) have a very regular pattern of blood vessels (green, "SeA") sprouting up, while embryos lacking Semaphorin-PlexinD1 signaling (right) have too many sprouts, with incorrect positioning.

Zygmunt, T., Gay, C., Blondelle, J., Singh, M., Flaherty, K., Means, P., Herwig, L., Krudewig, A., Belting, H., Affolter, M., Epstein, J., & Torres-Vázquez, J. (2011). Semaphorin-PlexinD1 Signaling Limits Angiogenic Potential via the VEGF Decoy Receptor sFlt1 Developmental Cell DOI: 10.1016/j.devcel.2011.06.033
Copyright ©2011 Elsevier Ltd. All rights reserved.

July 7, 2011

Totally tubular! If Bill and Ted had an excellent adventure in the human body, you can be certain that they’d learn about the most excellent tube structures throughout the body. From the veins that carry our blood to the branching tubules in our lungs, tubes are very important structures. A recent paper looks at the role of adhesion proteins during tubule formation.

During development, dramatic rearrangements of epithelial sheets results in the formation of branched tubules, as seen in kidney, lung, and mammary gland tissue. As one might expect, these rearrangements require coordination of several cellular events such as cell division, migration, polarization, and adhesion. A recent paper describes the role of two adhesion proteins, E-cadherin and cadherin-6, in tubule formation. Jia and colleagues found that cadherin-6 is important in inhibiting tubule formation, while E-cadherin is important in the formation of a tubule’s lumen (its inside cavity). Images above show the use of cell cysts as a model for epithelial tubule and lumen formation, with fluorescent tags showing a lateral marker (blue) and lumen-facing apical markers (green and red). Samples of control cysts, cysts without cadherin-6, E-cadherin, or both are shown (moving left to right). Although the mutant cysts appear abnormal, polarization was not disrupted in cysts without either cadherin (although multiple lumens are visible in cysts lacking E-cadherin). The polarization of cysts lacking both cadherins, however, was completely disrupted.

Jia, L., Liu, F., Hansen, S., ter Beest, M., & Zegers, M. (2011). Distinct roles of cadherin-6 and E-cadherin in tubulogenesis and lumen formation Molecular Biology of the Cell, 22 (12), 2031-2041 DOI: 10.1091/mbc.E11-01-0038