Journal Club: Neuroscience, Immunology, and Developmental Biology

NEUROSCIENCE: An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females. Correa, S.M., et al. (Ingraham, H.A.). Cell Rep. 2015. 10(1):62-74

Efforts to identify intrinsic, biological causes for differences in the behaviors typical of men and women (or boys and girls) must also carefully consider the role of culture. In mice, you can feel a lot safer about just pinning it on the biology.

Previous research has found that estrogen-receptor-alpha neurons in part of the ventromedial hypothalamus in the brain are essential for multiple sex-specific behaviors. Here, the authors found evidence that different subsets of these neurons control different behaviors.

Specifically, they identified Nkx2-1-expressing neurons that support locomotion in females; loss of these neurons leads to fatter, less active females. In contrast, this subset of neurons does not control fertility or brown fat thermogenesis, both of which are known to be dependent on estrogen-receptor-alpha neurons.

NEUROSCIENCE: Pharmacological induction of the 70-kDa heat shock protein protects against brain injury. Kim, N., Kim, J.Y., and Yenari, M.A Neuroscience. 2015. 284:912-919.

Life can be hard out there for a cell. Between extremes in temperature and solute concentrations, misfolding proteins and a host of other factors, things can get stressful. Fortunately, eukaryotes have many different heat shock proteins, which protect cells from some of these stresses.

Here, the authors reported on an investigation into how inducing one of these heat shock proteins (HSPs) affected the ability of an entire tissue to respond to injury. They began by demonstrating that injecting the drug 17-AAG led to increased HSP70 in microglia, a major type of cell in the nervous system.

They examined how treatment with 17-AAG affected how mice reacted to experimentally induced traumatic brain injuries. Promisingly, they observed that the treated mice had decreased bleeding and better neural function.

IMMUNOLOGY: JUNB is a key transcriptional modulator of macrophage activation. Fontana, M.F., et al. (Kim, C.C.). J Immunol. 2015. 194(1):177-186.

A successful immune response is a balancing act. It needs to be very sensitive to germs but not so sensitive it attacks the body. It needs to be strong enough to eliminate the infection but not so strong that it destroys healthy tissue.

In this article, Fontana and colleagues identified a control switch that helps regulate how macrophages, a type of white blood cell, react when they are activated. They first analyzed publicly available data high-throughput data to create a model for a macrophage regulatory network; their model included the transcription factor Junb.

They found that Junb is necessary for full expression of an important immune molecule that is produced during classical inflammation. At the same time, Junb also plays a role in so-called alternative activation of macrophages, which occurs, for example, during wound healing, indicating that this gene is an important general modulator of macrophage activity.

DEVELOPMENTAL BIOLOGY: Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast. Guzman-Ayala, M., et al. (Ramalho-Santos, M.). Development. 2015. 142(1):118-127.

Fetal growth during the last few months of pregnancy seems dramatic, but it pales in comparison to the rapid rate of growth that occurs in the first phases of development.

Cells very vigorously divide in the epiblast, an early stage of development. It has been hypothesized that such proliferation must require a very high rate of transcription, but how this high rate of transcription occurs was unknown. In this paper, Guzman–Ayala and colleagues reported one important driver.

They noticed that mice lacking Chd1 have decreased cell division and increased cell death in the epiblast. Further research showed that there was a genome-wide decrease in transcription in these cells. They found decreased binding of RNA Pol II to DNA and less ribosomal RNA.