February 26, 2013

Change is good.  This mantra isn’t good for just uptight type-As like me, but for embryos too.  Morphogenesis describes the physical changes that shape an organism out of a ball of cells, and is at the center of countless obsessions and questions of developmental biologists.  Today’s image is from a paper that helps us understand how a sheet of cells can form three-dimensional structures.

Morphogenesis describes the physical transformation and organization of cells into the shape of a developing organ or organism.  In the developing fruit fly egg, the epithelial layer of cells surrounding the egg chamber develops two dorsally projecting tubes, in which appendages used for gas exchange by the embryo form.  This transformation of a sheet of cells into a three-dimensional tube structure is not completely understood, but a recent paper describes the cell rearrangements involved.  Osterfield and colleagues used live imaging and three-dimensional reconstruction to show that the formation of the appendages is driven by epithelial sheet bending and a series of cell intercalations, which correlates with the localizations of myosin and the polarity protein Bazooka.  Using computational models, Osterfield and colleagues test how a pattern of line tensions in cell-cell edges in the epithelial sheet could drive three-dimensional changes.  The images above show fruit fly egg chambers during appendage formation (top row).  Three-dimensional reconstructions (bottom row) show the process from above (left) and the side (middle, right), with the arrow pointing to out-of-plane bending of the tissue.

ResearchBlogging.orgOsterfield, M., Du, X., Schüpbach, T., Wieschaus, E., & Shvartsman, S. (2013). Three-Dimensional Epithelial Morphogenesis in the Developing Drosophila Egg Developmental Cell, 24 (4), 400-410 DOI: 10.1016/j.devcel.2013.01.017 
Copyright ©2013 Elsevier Ltd. All rights reserved.

February 22, 2013

Although my muscles fail me if I try to pick up anything that weighs more than three pounds, I’m appreciative of their health and relative youth.  With so many complicated structures required for one single muscle to function properly, it is no wonder there is a long list of myopathies, or muscular diseases, that make life difficult for countless folks.  Thankfully, many biologists are here to help us understand muscle structure and function.

Muscles fibers are made of long chains of sarcomeres, the basic units of a muscle, which contract to allow for muscle function.  Costameres are structures that connect sarcomeres to the muscle cell’s plasma membrane, called the sarcolemma.  The disruption of this physical connection can cause several different myopathies.  A recent paper describes the role for a protein called obscurin in sarcolemma and costamere integrity.  According to Randazzo and colleagues, mice that were deficient in obscurin had altered localization of a muscle-specific adaptor protein called ankyrin isoform ankB at the M-line of sarcomeres, as well as an altered localization of the costamere-specific protein dystrophin at costameres.  The microtubule network at the sarcolemma was also disrupted in mice lacking obscurin.  These results are consistent with sarcolemma instability and reduced muscle exercise tolerance seen in these mutant mice.  In the images above, muscle fibers in mice lacking obscurin (bottom row) have reduced levels of dystrophin (red, left column) at costameres, while another costamere protein called β-dystroglycan (β-DG, red, middle column) appears unchanged.  The microtubule cytoskeleton (red, right column) in these mutant fibers is also disrupted.  (Z-disk protein α-actinin is in green in all images.)

ResearchBlogging.orgRandazzo, D., Giacomello, E., Lorenzini, S., Rossi, D., Pierantozzi, E., Blaauw, B., Reggiani, C., Lange, S., Peter, A., Chen, J., & Sorrentino, V. (2013). Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity originally published in the Journal of Cell Biology, 200 (4), 523-536 DOI: 10.1083/jcb.201205118

February 19, 2013

No matter how long you’ve been with your partner, sometimes he or she reveals a hidden talent that you’re just amazed to witness for the first time.  Maybe it’s his or her plate-spinning routine, amazing juggling, or a surprise skill at carving flowers out of radishes.  One day I will surprise my husband with my own hidden talent, once I find it, and he will wonder if it’s normal for one person to love another so much.  Today’s image is from a paper showing microtubules branching from existing microtubules…branching!  Is it normal for one person to love microtubules so much?!

Microtubules are dynamic filaments required in countless cellular processes, so their nucleation and growth has always been a point of interest for many biologists.  Microtubule nucleation from centrosomes is the best understood mechanism for microtubule nucleation, yet centrosomes are not always necessary for microtubule growth within a mitotic spindle.  A recent paper shows direct evidence for microtubule nucleation from existing microtubules in meiotic frog extracts, through the use of TIRF microscopy.  Petry and colleagues show that these new daughter microtubules nucleate from existing microtubules at a low “branch” angle.  In addition, daughter microtubules have the same polarity as mother microtubules, which can help maintain mitotic spindle integrity.   Branching microtubule nucleation requires γ-tubuin and augmin, a protein that increases microtubule density.  RanGTP, which is required for chromatin-mediated microtubule nucleation, and its effector protein TPX2 both stimulate branching microtubule nucleation.  In the images above, microtubules branch from existing microtubules after the addition of both RanGTP and TPX2, resulting in fan-like microtubule structures.  Lower panel is an enlarged view of the area marked with the asterisk.  Long arrows point to daughter microtubules nucleating at a clear branched angle, while short arrows point to daughter microtubules growing along the length of mother microtubules.

BONUS!!  Here's a mesmerizing movie of branching microtubules after the addition of RanGTP and TPX2, similar to the above image.
video

ResearchBlogging.orgPetry, S., Groen, A., Ishihara, K., Mitchison, T., & Vale, R. (2013). Branching Microtubule Nucleation in Xenopus Egg Extracts Mediated by Augmin and TPX2 Cell, 152 (4), 768-777 DOI: 10.1016/j.cell.2012.12.044 
Copyright ©2013 Elsevier Ltd. All rights reserved.

February 15, 2013

The regulation of genes occurs at many levels, one of the first of which is physical access to a gene.  The way DNA is packaged may or may not allow transcription machinery from even getting to an area of the genome.  Understanding these modifications in each cell type and location is important, but difficult within a tissue or tumor of different cell types.  A recent paper tackles this problem with a new method.

Histones are proteins that package DNA to condense its size and to aid in gene regulation.  Histones can be modified in many different ways, and these modifications affect how accessible or inaccessible a certain region of the genome is to gene transcription.  Chromatin immunoprecipitation, the current technique to understand histone modifications at different gene sites, does not provide information on histone modifications of single cells within a complex environment of different cell types.  A recent paper describes a new technique that allows the visualization of histone modifications at single-cell resolution within a fixed tissue.  Using this technique, Gomez and colleagues tracked one specific histone modification, dimethylation of lysine 4 of histone H3 (H3K4me2) at the genetic loci for MYH11 in smooth muscle cells (SMC).  SMC-containing tissues contain other cell types, and even non-SMC tissues contain some SMCs due to vascularization.  In the images above, MYH11 H3K4me2 modifications (red, arrows) were found only in SMCs (green cells) in sections of human carotid artery tissue (DNA in blue).  Higher magnification images are bottom row.

ResearchBlogging.orgGomez, D., Shankman, L., Nguyen, A., & Owens, G. (2013). Detection of histone modifications at specific gene loci in single cells in histological sections Nature Methods, 10 (2), 171-177 DOI: 10.1038/nmeth.2332
Adapted by permission from Macmillan Publishers Ltd, copyright ©2013 

February 12, 2013

The endoplasmic reticulum (ER) is my kind of organelle for its dynamic nature and sorting abilities.  If you could see my pantry, desk, or closet then you’d know that a life of sorting and organizing is my jaaaaam.  Today’s image is from a paper identifying a regulator of ER dynamics.

The endoplasmic reticulum (ER) is a dynamic, interconnected network of membrane vesicles, cisternae (sac-like structures), and tubules.  The ER serves many functions, including protein synthesis (on the rough ER), protein folding, and protein sorting.  The ER experiences complex rearrangements, and a recent paper identifies Rab10 as a regulator of these ER dynamics.  Rab10 is a Rab GTPase, a family of membrane proteins that function as molecular switches for many membrane-based events such as vesicle formation and fusion.  English and Voeltz found that Rab10 is found on the ER and on ER-structures involved in new ER tubule growth.  Depletion of Rab10, or expression of a mutant Rab10, caused a disruption of ER morphology, as well as reduced ER tubule extension and fusion.  In the images above, cells were labeled with an ER marker.  Compared to controls cells, Rab10-depleted cells had an altered ER morphology, notably more expansive cisternae and fewer tubules.

English, A., & Voeltz, G. (2012). Rab10 GTPase regulates ER dynamics and morphology Nature Cell Biology, 15 (2), 169-178 DOI: 10.1038/ncb2647 
ResearchBlogging.orgAdapted by permission from Macmillan Publishers Ltd, copyright ©2013

February 7, 2013

The alphabet soup of cell biology can be overwhelming, but APC is one jumble of letters that most cell biologists are very familiar with.  APC is a protein that functions in cell division and development, and is the most commonly mutated gene in colon cancer.  Today’s image is from a paper describing another hat that APC gets to wear—a role in the interaction between microtubules and intermediate filaments.

Intermediate filaments (IFs) and microtubules are both part of the cell’s cytoskeleton, and their interactions together during different cellular processes have brought attention to the possible proteins that guide these interactions.  IFs function in cell migration, and a recent paper describes rearrangements of the IF network during the migration of astrocytes, cells that provide nutritional and structural support for neurons in the brain.  Sakamoto and colleagues found that the tumor suppressor protein APC (adenomatous polyposis coli) is required for microtubule-IF interactions and for the microtubule-based rearrangements of the IF network in migrating astrocytes.  Loss of APC resulted in a disorganized IF network in glioma and carcinoma cells.  The images above show microtubule-APC-IF interactions in a migrating astrocyte, with fluorescently labeled IFs (vimentin, green), APC (red), and microtubules (blue).  Arrowheads point to APC along microtubules, while arrows point to both IFs and APC along microtubules.

ResearchBlogging.orgSakamoto, Y., Boeda, B., & Etienne-Manneville, S. (2013). APC binds intermediate filaments and is required for their reorganization during cell migration originally published in the Journal of Cell Biology, 200 (3), 249-258 DOI: 10.1083/jcb.201206010

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.

ResearchBlogging.orgMa 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