Journal Club: Neuroscience, Biochemistry, Immunology, and Developmental Biology

NEUROSCIENCE: Radial glia required PDGFD-PDGFRβ signaling in human but not mouse neocortex. Lui, J.H., et al. (Oldham). Nature. 2014. 515(7526):264-268.

How did humans evolve their particular mental abilities? What genetic changes make us distinct from other animals? A recent paper by Lui and colleagues provides a small step toward the answers to those questions.

Humans have a relatively much larger neocortex than mice. This larger neocortex has been hypothesized to be due to more proliferation by radial glia. Here, the authors compared the gene expression of radial glia in human and mouse and found production of the growth factor PDGFD only in human.

In follow-up experiments, they found expression of the receptor for PDGFD in parts of the human neocortex. They also demonstrated that inhibition of this signaling in human slice culture prevents normal proliferation of radial glia, and that adding PDGFD to developing mice neocortex increases the number of radial glia.

BIOCHEMISTRY: Enhancer interaction networks as a means for singular olfactory receptor expression. Markenscoff-Papadimitriou, E., et al. (Lomvardas). Cell. 2014. 159(3):543-557.

The sense of smell relies on expression of olfactory receptors by a select population of neurons. Each of these neurons expresses only one out of a few thousand possible olfactory receptor (OR).

Previous research has demonstrated much of the feedback loop that maintains expression of a particular OR and prevents transcription of others. In this article, the Lomvardas group provide insight into how transcription of a particular OR gets started in the first place.

They used epigenetic analysis to identify putative OR enhancers and gain- and loss-of-function experiments to demonstrate activity by 11 of them. Additional experiments showed that although a single OR is important in establishing open chromatin at a particular OR, convergence of multiple OR enhancers, including ones on other chromosomes, occurs at an OR gene that is being expressed.  

IMMUNOLOGY: Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation. Nabekura, T. and Lanier, L.L. J Exp Med. 2014. 211(12):2455-2465.

Natural killer cells are a type of white blood cell that combat viral infections and can play a role in transplant rejection. Recent research has shown that natural killer (NK) cells can differentiate into long-lived memory NK cells after stimulation.

The only existing mouse model for memory T cells so far has been MCMV infection. Here, Nabekura and Lanier demonstrate memory NK cells can also be generated in response to foreign mouse cells.

Some NK cells from the B6 strain of mice recognize a protein found in the Balb/c strain of mice. In an inflammatory setting, NK cells with an activating receptor recognizing this protein proliferated and could differentiate into memory cells. Interestingly, a subset of NK cells with this activating receptor also had an inhibitory receptor that recognized the same protein and could prevent proliferation.

DEVELOPMENTAL BIOLOGY: Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain. Arnold, T.D., et al. Development. 2014. 141(23):4489-4499.

The blood vessels in the brain are particularly tight, restricting in what can get in and out, in what is called the blood–brain barrier. Previous research on brain vascular development has focused on factors that promote blood vessel formation but not so on role of factors that suppress it.

In this paper, the authors researched the effect of loss of the integrin αVβ8 on brain blood vessel development. They found that this integrin normally activates TGFβ gradients that inhibit new vessel formation and loss of this integrin leads to cerebral hemorrhage.

By comparing these mice to another mutant mouse that also has problems with its CNS vasculature, they concluded that it was the abnormal vessel sprouting itself, and not the blood-brain barrier disruption that followed, that led to the hemorrhage.