Journal Club: What may be the difference between cochleae of humans, mice and marmosets? Focus on Connexin/Pannexin

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Today's journal article

Hosoya M, Suda S, Ueno M, Shimanuki MN, Nishiyama T, Oishi N, Ozawa H. "Distinct Connexin43, Connexin31, and Pannexin1 expression patterns in the cochlea of a non-human primate."

Why I picked this article

This publication investigates proteins in the cochlea, our inner ear organ, using the marmoset as the animal model. 

When I was a research fellow in Japan, I had the privilege of visiting the marmoset breeding facility to collect eyes from marmosets. The common marmoset is a New World monkey. They are slightly less related to humans compared to an alternate primate model like macaca. However, the common marmoset has faster gestation periods and commonly gives birth to twins, which makes it advantageous for propagation, which is important for biomedical research use. 

Primate models are, without doubt, challenging to use for biomedical research with ethical considerations. However, it is also true that some primate-only features could be critical for some research. For example, in the vision system, colour vision is the same as that of us humans, and the presence of fovea (an area where the nerve for vision systems is clustered together) in primates, but absent in non-primates, makes the use of primates still very relevant and important. 

For our auditory system, the cochlea is a mammalian feature. I'm not sure yet what the list of "primate-only features" might be. My feeling is that as we expand comparisons from mice (and other small animals), humans, non-human primates, and non-primate large animals, we will start to separately identify many "large animal-specific features" and "primate-only features" that may exist. I am very excited about the possibility of finding some of these features through our research using sheep as the large animal model, and consequently, drawn to primate studies like this publication. 

Figure: How do you pick your animal model?? (created using Biorender.com)

Some of the research findings

This study searched for proteins called Connexin 43 (Cx43), Connexin 31 (Cx31) and Pannexin 1. 

Marmoset temporal bones (= part of the skull containing the inner ear) were collected from:

  • E101 (gestation day 101/150)
  • E109 (gestation day 109 /150)
  • E120 (gestation day 120/150)
  • P0 (birth)  

Antibodies (used for finding these proteins):

  • Connexin 43 (Rabbit IgG, ab11370, Abcam, Cambridge, UK, 1:500) 
  • Connexin 31 (Rabbit IgG, 12880-1-AP, Proteintech, 1:100)
  • Pannexin 1 (Rabbit IgG, ACC-234, Alomone labs, Jerusalem, Israel, 1:500) 
  • Of course, other antibodies are also used to label different cell types. 

Connexin 43:

  • In the mature cochlea, Connexin 43 in this study was found in basal cells of the stria vascularis and type I spiral ligament fibrocytes (= both very important for homeostasis of the cochlea, and help them traffic certain ions within the cochlea). This pattern is the same as previously reported in mice and human cochleae. 
  • Connexin 43 did not colocalise with connexin 26, an observation also shared with mice. 
  • The timing of Connexin 43 starting to be produced seemed to coincide with when basal cells are maturing. 

Connexin 31: 

  • In the adult marmoset cochlea, Connexin 31 was found in the spiral ligament fibrocytes, basal cells of the stria vascularis, and in some supporting cells. This pattern is different to what has been reported in mouse cochleae. 

Pannexin 1:

  • In this study, the authors found pannexin 1 in the spiral ligament fibrocytes and satellite cells in the spiral ganglion (= area where you find a lot of auditory neuron cell bodies). Satellite cells hug auditory neurons. This is again different to what has been reported previously in mouse cochleae. 

Haruna's takeaway

This is a very concise publication with a lot of beautiful microscopy images. I always like literature with nice microscopy... 

There appear to be quite a few places where proteins are found differently between the common marmoset and mice. In the introduction, the authors note that previous research has found differences between the cochleae of rodents and the cochleae of marmosets with regard to other connexin proteins. As the authors note, this is very interesting given how important connexin proteins are for the homeostasis of the cochlea and our sense of hearing. 

For Connexin 43, it appeared to be found in a similar manner between the rodent and the marmoset cochlea. It's also interesting to note that Cx43 is widely distributed in other organs, including the eyes and organs like the heart; perhaps due to its importance, connexin 43 is more conserved between species. 

The finding relates to the research interest of us and others on purinergic signalling (= a type of signalling pathway, mediated by a molecule called ATP). Connexins and pannexins form channels that can release ATP as part of the purinergic signalling pathways. There may be relevance of cross-species variation that researchers have observed about connexins, in the context of  ATP-mediated signalling. This may particularly apply to, for example, the pannexin 1 found in satellite cells in the marmoset cochlea in this study. 

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This is Haruna's 6/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.