Wednesday 31 July 2013

Exosomes



Endosomal pathways from Danzer et al. (here) © 2012 Danzer et al.

Exosomes are tiny vesicles (50-100 nm) released from living cells. They represent a hitherto overlooked route of intercellular communication. Exosomes were the focus of a symposium at the CTR Annual Meeting at Cambridge earlier this month.

The precursors to exosomes are intralumenal vesicles (ILVs), which are found in multivesicular bodies (MVBs) or "late endosomes." ILVs are formed by invagination of the outer membrane of the MVB. Thus initially they contain cytosol. However, the ILV outer membrane can be restructured by a scramblase and both proteins and lipids can be sorted into the ILVs before they are released as exosomes. Recently the focus has been on the direction of microRNAs into exosomes. The argument convincingly presented at Cambridge was that exosomes once released act as carriers to take proteins, lipids and RNAs to target cells. Their contents are released to the target cell following fusion of the exosome with its plasma membrane or uptake of the complete exosome. One of the speakers at Cambridge was Michel Record whose previous review (here) can be recommended. 

Multivesicular bodies are a prominent feature of the guinea placenta (here). They are associated with a system capable of taking up maternal proteins and transporting them to the fetal circulation. The potential role of exosomes in this context deserves to be explored. Could they be involved in the transfer of intact maternal antibodies that confers passive immunity on the fetus?

Tuesday 23 July 2013

Amo's chapter on placentation

Amo Cambridge 1972

Emmanuel Ciprian Amoroso FRS (Amo) is best remembered for his monumental chapter on Placentation written for the 1952 edition of Marshall's Physiology of Reproduction edited by A. S. Parkes (Volume II pages 127-309).

Amo was born in Trinidad and graduated in medicine from the National University of Ireland. He then spent 1930-32 in Germany and his knowledge of the German literature (almost unread in the English speaking world) was one reason his chapter was so important.

Amo then came to University College London where he completed his Ph.D. under the auspices of J. P. Hill. From there he moved to the Royal Veterinary College where he was Professor of Veterinary Physiology from 1950 to his retirement in 1968. Amo was a mentor for many scientists with distinguished careers. He continued in this role on retirement when he found a new home at the Institute of Animal Physiology at Babraham near Cambridge. He died in 1982.

An engaging account of Amo's life was written by R. V. Short (here). The true monument remains his chapter which has a place of honour on my bookshelf.

Tuesday 16 July 2013

How large were the first placentals?

Dinosaurs and insectivores
Colbert (1955) Evolution of the Vertebrates

Were the first placentals (mammals other than marsupials and monotremes) tiny animals living in the shadow of the dinosaurs? The idea predates cladistics and molecular phylogenetics (see above). Most fossils from the Mesozoic are indeed small.

A recent study (here) took another approach based on the fact that there is a faster divergence in GC3 in long-lived species than in short-lived ones (GC3 is the percentage of guanine and cytosine at the third position of gene codons). Body size correlates to longevity.

The authors constructed a tree based on the genomes of 33 placentals with two marsupials and a monotreme as outgroups. They then estimated the ancestral GC3 at each node of the tree including the most recent common ancestor of placentals. From this last value they could estimate the longevity and body mass of early placentals. The surprising result was they had a life span above 25 years and a body mass above 1 kg (less if arboreal).

Looking at mammals as a whole (not just eutherians/placentals and metatherians/marsupials), the fossil record offers several examples of medium to large mammals such as Sinocondon from the Jurassic and Repenomamus from the Early Cretaceous (elegantly reviewed by Luo here). It is not beyond the bounds of possibility that the most recent common ancestor of placentals was in a similar size range.

Tuesday 9 July 2013

Ossification patterns and the phylogeny of mammals

Afrotherian embryos. Reproduced from Hautier et al. (here)
© 2013 The Authors

High resolution X-ray microtomography is among new methods available to comparative anatomists. It enables non-invasive imaging of museum specimens and subsequent 3D visualisation of the tissues. One field where it has been applied is to study the sequence in which bones become ossified during embryonic and fetal development.

An obvious requirement is that developmental series are available as for the African elephant (here) and tail-less tenrec (here). A new study from the Department of Zoology at Cambridge (here) analyzes data from a wider range of afrotherians. It then compares ossification patterns in "southern" mammals (Afrotheria and Xenarthra) and "northern" mammals (Laurasiatheria  and Euarchontoglires).

The "northern" mammals share a common ancestor (together constituting Boreoeutheria). There is little variability in developmental sequences between species available for study. In contrast both groups of "southern" mammals exhibit shifts in ossification sequences. At first sight this might seem to argue for a common ancestor for Afrotheria and Xenarthra. However, the shifts are different in the two clades and this could argue against a common ancestry.

The data are intriguing as we still lack certainty about the root of the tree. This is largely because the four major clades diverged so rapidly early in the history of placental mammals. Even phylogenomics has yielded conflicting results (discussed here).


Thursday 4 July 2013

Placentation in the koala

Koala (Phascolarctos cinereus) 
Photo by David Iliff. License: CC-BY-SA 3.0

The koala (Phascolarctos cinereus) is a member of Vombatidae and its fetal membranes resemble those of the wombats (previous post).
Fetal membranes of the koala from Caldwell (1884)

In fact adherence of the allantois to the chorion was first described for this marsupial (here). Richard Semon soon suggested that this combination of yolk sac and simple chorioallantoic placentation was present in the common ancestor of marsupials and placentals. In other marsupials the chorioallantoic placenta was lost (bandicoot placentation had not then been described); in placentals the chorioallantoic placenta was elaborated and the yolk sac reduced or lost. In recent times this idea was revived by Freyer, Zeller and Renfree (here).

There is little of recent date though the koala is included in a review by Hughes (here) as well as a later book chapter. Based in part on the Hill Collection it includes histology of the yolk sac placenta and gross morphology of the chorioallantoic placenta.

Updated 17 July 2013