April 29, 2013

There are many, many things in cell biology that can serve as models for fine art, but fewer are more stunning to me than a Purkinje neuron.  Purkinje neurons are some of the largest neurons in the brain, where they participate in motor control from the cerebellum.  Today’s image is from a paper describing what happens when a protein called rictor is depleted from Purkinje neurons.

The two multi-protein complexes mTORC1 and mTORC2 share sensitivity to inhibition by the immunosuppressive drug rapamycin, yet likely have distinct roles in cell function and development.  Each complex is composed of a distinct set of subunits—mTORC1 depends on the protein raptor, while mTORC2 depends on the protein rictor.  A recent paper describes an important role for mTORC2 in neuron size, morphology, and function.  Thomanetz and colleagues found that two different mouse lines lacking the mTORC2 protein rictor had smaller neurons with disrupted function, likely mediated through regulation of PKC (protein kinase C) isoforms.   mTORC1 activity was unaffected in these mutants.  When rictor was depleted from the entire central nervous system, motor function of the mice was affected.  When rictor was depleted from only Purkinje neurons, the cell type with the highest rictor expression, neurons were smaller and their morphology was abnormal.  In the images above, control Purkinje neurons (top) had only one primary dendrite compared with neurons lacking rictor (bottom), which had multiple primary dendrites (notated in different colors, right).  

Thomanetz, V., Angliker, N., Cloetta, D., Lustenberger, R., Schweighauser, M., Oliveri, F., Suzuki, N., & Ruegg, M. (2013). Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology originally published in the Journal of Cell Biology, 201 (2), 293-308 DOI: 10.1083/jcb.201205030

April 26, 2013

It’s Worm Week here at HighMag Blog.  Worms are amazing little creatures, and the species C. elegans is an invaluable model system for studying cell and developmental biology.  Their genome is sequenced, their development is precise and well-documented, and their bodies and embryos are translucent (making them photogenic under a microscope).  Today’s image is from the same lab that brought Tuesday’s image…worm gonads rock!

Blurb and image from Christian R. Eckmann:
The image is an immuno-stained part of an extruded C. elegans hermaphrodite gonad; germ cell nuclei (magenta) and the apical membrane (green). The germ stem cells reside at the closed end of this tube like tissue. In wild type, the germ stem cells exit the mitotic zone, entering meiosis further away from the closed tip and start differentiating into sperm or oocytes. 

The image posted earlier this week is from the Gracida and Eckmann paper that identifies a nuclear receptor that protects germ stem cell integrity, and in turn fertility, after dietary perturbations.

Gracida, X. & Eckmann, C. (2013). Fertility and Germline Stem Cell Maintenance under Different Diets Requires nhr-114/HNF4 in C. elegans Current Biology, 23 (7), 607-613 DOI: 10.1016/j.cub.2013.02.034 

April 23, 2013

I’m thankful that my body knows how to handle days when I feed it wonderful things, like a banana and a giant bowl of strawberries, then follow it up with a few gut-busting mini-doughnuts.  Although worms and other organisms don’t have access to doughnuts like I do, their bodies still have protections in place to handle changes in their diet.  Today’s image is from a paper describing how the germline is protected from a changing diet.

Organisms consume a variety of food options, yet their bodies know how to regulate these changes to maintain homeostasis, all the way down to the cellular level.  A recent paper shows how an organism’s germline stem cells (GSCs), the source of eggs and/or sperm, are protected from food intake.  Gracida and Eckmann found that the nuclear receptor NHR-114 protects GSCs from dietary perturbations in worms, possibly through a detoxifying response to certain food intake.  Without NHR-114, worms on certain bacterial diets become sterile due to germ cell division defects during development.  The dietary sensitivity is based on intake of the amino acid tryptophan.  In the images above, gonads of worms fed a certain bacterial diet are stained to see individual germ cells (cell cortex staining in green in merged; DNA is purple).  Compared to wild-type worms (left), worms depleted of NHR-114 (right) have germ cell defects, notably cells with multiple nuclei (arrowhead).

Gracida, X., & Eckmann, C. (2013). Fertility and Germline Stem Cell Maintenance under Different Diets Requires nhr-114/HNF4 in C. elegans Current Biology, 23 (7), 607-613 DOI: 10.1016/j.cub.2013.02.034 
Copyright ©2013 Elsevier Ltd. All rights reserved. 

April 16, 2013

I’m as type-A as a person can get, with my organized desk, to-do lists, and inability to roll with it (I sound dreadful, right?).  One thing that will never change is the calm I feel when I read the word “systematic” in a paper’s title or abstract.  Anything done systematically soothes me like a heartbeat soothes a newborn.  Today’s image is from a paper that uses a—you guessed it—systematic approach to understanding the roles of dynein and its many regulators in mitosis.

Dynein is a large microtubule motor complex that is important in countless cellular processes, most notably mitosis.  Like most proteins, dynein relies on numerous adaptor proteins and the dynactin complex to help localize the motor and/or activate it.  A recent paper uses siRNA screening to systematically test the roles of dynein subunits, adaptor proteins, and dynactin subunits to build a more complete picture of the roles of each protein in mitosis.  Raaijmakers and colleagues show that while some regulators are required for activation but not localization of dynein, others are required mainly for dynein localization.  Dynactin, for example, is not necessary for spindle organization, but rather serves as a dynein recruitment factor at the nuclear envelope and kinetochores.  In the images above, the mitotic spindle in a control cell is very focused at spindle poles (second row, green in merged).  When the dynein heavy chain subunit is depleted from cells (all other columns), spindles show a range of spindle pole focusing defects, including spindles lacking attachment to their poles.  Spindle microtubules are top row, red in merged; chromosomes are third row, blue in merged.

Raaijmakers, J., Tanenbaum, M., & Medema, R. (2013). Systematic dissection of dynein regulators in mitosis originally published in the Journal of Cell Biology, 201 (2), 201-215 DOI: 10.1083/jcb.201208098

April 12, 2013

I think I speak for many when I say that dinosaurs were the first objects of our life-long science obsessions.  Their size, history, and ferocious good looks fascinate even the youngest preschoolers.  Although my obsession turned to microscopic things, some folks remained true to their love of dinosaurs and history.  Today’s image is a treat, and a great example of how the basic questions in developmental biology know no timeline.

The study of dinosaur embryos at the cellular levels helps scientists understand the growth patterns of dinosaurs.  Despite this, little is known about dinosaur embryos, as they are rare and typically still inside of their eggshells.  A recently discovered dinosaur embryo bone bed in China is the oldest dinosaur embryo find in fossil record, from the Lower Jurassic about 190-200 million years ago.  These embryos represent several different nests, and are at different developmental stages.   In addition, these embryos are likely that of a Lufengosaurus, from the sauropodomorph clade of dinosaurs known for long necks and gigantism.  Because of the variation of age of these found embryos, Reisz and colleagues were able to track development through several different stages, including very early embryonic stages.  In the images above, thin sections from three different femur (thigh) bone samples (of 24 discovered total) show changes in the bone tissue formation as the embryos age from youngest (left) or oldest (right).  Two different regions of the femora are shown for each sample (top and bottom).

BONUS!  More thin sections are shown below.

Reisz, R., Huang, T., Roberts, E., Peng, S., Sullivan, C., Stein, K., LeBlanc, A., Shieh, D., Chang, R., Chiang, C., Yang, C., & Zhong, S. (2013). Embryology of Early Jurassic dinosaur from China with evidence of preserved organic remains Nature, 496 (7444), 210-214 DOI: 10.1038/nature11978 
Adapted by permission from Macmillan Publishers Ltd, copyright ©2013 

April 9, 2013

Our genome is chock full of so many things that aren’t even genes.  In fact, only about 2% of the human genome actually encodes protein sequences...mind blown, right?!  There are many different kinds of elements and domains within our genome that regulate gene expression through their roles in chromosome architecture and organization.  Today’s image is from a paper that describes the dynamics of one type of domain—the lamina associated domain.

The nuclear lamina is a protein layer that coats the inside nuclear membrane, and serves to anchor chromosomes.  Regions in the genome called lamina associated domains (LADs) specifically associate with the nuclear lamina.  LADs cover about 35-40% of the genome, suggesting that they may affect chromosome position and architecture.  A recent paper tracks LAD-nuclear lamina interactions throughout the cell cycle in single cells.  Kind and colleagues show that about 30% of LADs are positioned at the nuclear periphery.  LADs are stochastically positioned after mitosis, meaning that their position is not directly inherited.  In addition, these contacts are linked with gene expression and histone modifications.  In the images above, the nuclear lamina (blue) and mitotic spindle (red) are shown throughout the different stages of mitosis.  LADs (green) are rounded and at the nuclear periphery during prophase, and then become banded along chromosomes once the nuclear envelope breaks down (prometaphase and metaphase).  During cytokinesis, LADs are seen within the nucleus, but not yet positioned at the periphery.

Kind, J., Pagie, L., Ortabozkoyun, H., Boyle, S., de Vries, S., Janssen, H., Amendola, M., Nolen, L., Bickmore, W., & van Steensel, B. (2013). Single-Cell Dynamics of Genome-Nuclear Lamina Interactions Cell, 153 (1), 178-192 DOI: 10.1016/j.cell.2013.02.028
Copyright ©2013 Elsevier Ltd. All rights reserved.

April 5, 2013

Cell adhesion is sticky business.  See what I did there?!  Comedy. Gold.  Seriously, though, cell adhesion is complicated, with many types of cell adhesion structures that form at specific regions of the cell at specific times.  As important as it is to understand cell adhesion and its role in development, cancer, and normal cell function, we are all thankful for papers like the one that today’s image comes from.

Cadherins are transmembrane proteins that form cell-cell adhesion structures called adherens junctions.  There are several types of adherens junctions, but they are all composed of clusters of cadherins whose extracellular domains interact with other cells’ cadherins and intracellular domains interact with the cell’s cytoskeleton.  Individual cadherin molecules provide negligible adhesive properties, so understanding how cadherin clusters form is an important question.   A recent paper delves into the details of this process, and finds that actin filaments are indeed necessary for cadherin cluster stability.  Hong and colleagues found that cadherin clusters that were uncoupled from actin were unstable and exhibited random mobility.  When the actin-binding domain of a cadherin-actin adaptor protein called α-catenin (domain called αABD) was coupled to these mutant cadherin structures, the adhesive clusters regained stability and deliberate mobility.  The images above show clusters of this αABD-cadherin chimera (left, green in merged) associated with actin filaments (middle, red in merged; arrows in inset point to colocalization).

Hong, S., Troyanovsky, R., & Troyanovsky, S. (2013). Binding to F-actin guides cadherin cluster assembly, stability, and movement originally published in the Journal of Cell Biology, 201 (1), 131-143 DOI: 10.1083/jcb.201211054

April 2, 2013

As I write this, I have dirt underneath my fingernails and I love it.  Spring is here, and I have begun playing in the dirt and cheering for my budding vegetable garden seedlings.  I love the food plants provide us, but they’re also fascinating models for understanding cell biology and developmental biology.  Today’s image is from a paper identifying a player in the development of stomata, which are important plant organs.

Stomata are pore organs on leaves that regulate gas and water vapor exchange in plants.  They are made of pairs of guard cells that regulate the size of the stomata openings to let air in and oxygen out.  A recent paper describes the identification of a protein that regulates the maturing and functioning of stomatal guard cells.  Negi and colleagues identified SCAP1, a transcription factor, that when mutated results in irregularly-shaped guard cells.  These mutants also lack the ability to control stomatal opening and closing.  SCAP1 regulates the transcription of known guard cell development genes.  The images above show a wild-type plant (top) with normal developing stomata at all stages (mature stomata is right-most image).  In a scap1 mutant (bottom), however, later stages of stomata development are defective and result in stomata with a floppy or irregular appearance.

Negi, J., Moriwaki, K., Konishi, M., Yokoyama, R., Nakano, T., Kusumi, K., Hashimoto-Sugimoto, M., Schroeder, J., Nishitani, K., Yanagisawa, S., & Iba, K. (2013). A Dof Transcription Factor, SCAP1, Is Essential for the Development of Functional Stomata in Arabidopsis Current Biology, 23 (6), 479-484 DOI: 10.1016/j.cub.2013.02.001
Copyright ©2013 Elsevier Ltd. All rights reserved.