March 27, 2014

You might think of your bones as unchanging, but they are far more dynamic than you think. Today’s image is from a paper identifying a new blood vessel subtype found in the mouse skeletal system.

Osteogenesis is the formation of new bone tissue, and is important in bone renewal and fracture healing. Recent work suggests that osteogenesis may depend on the presence of blood vessels. A recent paper identified a new capillary subtype found in the mouse skeletal system. Kusumbe and colleagues found that these microvessels mediate growth of bone vasculature, and couple osteogenesis with angiogenesis (the formation of new blood vessels). These vessels and their associated osteoprogenitors were reduced in older bone, yet the reversal of this decline allowed bone mass renewal. In the images above, the microvessels (green) have a branched organization in a juvenile mouse tibia (arrowheads point to interconnections).

Kusumbe, A., Ramasamy, S., & Adams, R. (2014). Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone Nature, 507 (7492), 323-328 DOI: 10.1038/nature13145
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

May 9, 2013

When we think of wounds, we don’t typically think of them as part of normal, healthy function.  Micro-wounds, however, form when white blood cells have to cross the barrier in our blood vessels to get to an injury or infection.  These micro-wounds happen all the time, and our cells heal these wounds efficiently and elegantly.

One of the most important barriers in our body is that created by the vascular endothelium.  Vascular endothelial cells line all of our blood vessels—from the largest vessels to the smallest capillaries—and function in fluid filtration, hormone trafficking, and recruitment and trafficking of blood and stem cells.  The movement of cells, for example white blood cells, across the vascular endothelium and out of circulation creates “micro-wounds” that can compromise the integrity of the tissue.  A recent paper describes how these micro-wounds are healed, based on a model in which the vascular endothelium senses a loss of tension upon micro-wounding and triggers its own repair.  Martinelli and colleagues tracked micro-wounds that were created by either transmigrating white blood cells or by mechanical disruption by a probe, and found that ventral lamellipodia are generated by endothelial cells to close the micro-wounds.  These lamellipodia are enriched in Rac1 effector proteins, and require reactive oxygen species (ROS) and Arp2/3 for efficient wound closing.  Images above show probe-induced wounding of an endothelial cell, followed by wound healing.  The wound initially expanded to 20um across (80 seconds), with multiple nodes of ventral lamellipodia (blue arrowheads) and ventral F-actin waves forming around the wound and closing it.

Martinelli, R., Kamei, M., Sage, P., Massol, R., Varghese, L., Sciuto, T., Toporsian, M., Dvorak, A., Kirchhausen, T., Springer, T., & Carman, C. (2013). Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds originally published in the Journal of Cell Biology, 201 (3), 449-465 DOI: 10.1083/jcb.201209077

February 4, 2013

The brain needs blood like Beyonce needed pants at last night’s SuperBowl Halftime show.  (Side note, I think she was and looked amazing, but seriously…pants!)  Today’s image is from a paper describing the development of the blood vessel network in the brain.

The brain depends on an intricate network of blood vessels to supply the brain with oxygen and nutrients, but how the network forms during development is not well-understood.  A recent paper describes how radial glial cells play an important role in blood vessel formation and growth.  Radial glial cells are a type of stem cell in the developing brain and function in neurogenesis.  Ma and colleagues ablated radial glial cells during late embryonic development of the brain’s cerebral cortex and found that blood vessels regressed.  Radial glial cells interact with and stabilize new blood vessels, through use of the Wnt signaling cascade.  The images above show the cortical plate of a developing mouse’s brain at different stages.  Increasing blood vessel growth (green) can be seen from E14.5 (embryonic day 14.5) through E17.5.

Ma S, Kwon HJ, Johng H, Zang K, & Huang Z (2013). Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of wnt signaling. PLoS biology, 11 (1) PMID: 23349620

September 13, 2012

I’m sure you've been here before….you’re at a family gathering, and some distant relative or in-law hears that your research involves worms, flies, or yeast. You are snidely asked what use it is to do research on that, and then asked what kind of job you could actually get with that kind of background. This happened to me (at a funeral), but I didn’t have either the speed or the smugness to rattle off the list of diseases understood or medications developed thanks to these kinds of organisms. Next time, I’ll just pass out a copy of the paper that today’s image comes from—booyah!

Throughout evolution, many genes are coopted for use in diverse organisms. Recently, the gene network that maintains the cell wall in yeast, a fungus, was discovered to also play a role in vertebrate angiogenesis. Angiogenesis is the growth of blood vessels from pre-existing vessels, and is an important step in transforming a tumor into a spreading, malignant cancer. The same research group that realized this yeast-angiogenesis link suggested that drugs affecting the yeast cell wall may also function as angiogenesis inhibitors for chemotherapy. Cha and colleagues found that an inexpensive antifungal drug called thiabendazole could block angiogenesis in animal models and human cells. Specifically, the drug disassembles newly-sprouted blood vessels. When Cha and colleagues grafted human tumors into mice, they found that thiabendazole treatment slowed tumor growth and limited growth of the vascular network. In the images above, the network of blood vessels in a Xenopus frog embryo is disrupted after thiabendazole treatment (bottom), compared to a wild type embryo (top).

Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, & Marcotte EM (2012). Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent. PLoS biology, 10 (8) PMID: 22927795

September 6, 2012

Next time you are cursing your yard for having to prune your bushes, just take a cold sip of lemonade and know that you are helping your shrubs thrive. Or, you are just making them all look like green meatballs, like my shrubs. Win-win! Pruning is an essential part of development, and a recent paper shows pruning of the vasculature in the developing zebrafish brain.

Our brains are surrounded by a complex network of blood vessels that deliver oxygen and nutrients to the neurons. Although the existence of this vasculature has long been appreciated and studied, it has not been clear how the network is formed during development. A recent paper uses confocal live imaging to track the development of the vessel network in the developing zebrafish midbrain. Chen and colleagues found that the zebrafish brain undergoes both blood vessel growth and pruning during development. Blood vessel pruning is driven by blood flow—decreased blood flow triggers pruning, while increased blood flow impairs pruning. In the images above, a segment of blood vessel from the midbrain vasculature undergoes pruning (red arrow).

Chen Q, Jiang L, Li C, Hu D, Bu JW, Cai D, & Du JL (2012). Haemodynamics-driven developmental pruning of brain vasculature in zebrafish. PLoS biology, 10 (8) PMID: 22904685