Fig. left: Schematic outline of some key events during
pre-implantation mouse development to illustrate terminology (adapted from
L. Selwood and
M.H. Johnson (2006) Trophoblast
and hypoblast in the monotreme, marsupial and eutherian mammal: evolution and
origins. BioEssays, 28, 128-145).
P = pluriblast,
E = epiblast,
T = trophoblast subdivided into
PT = polar trophoblast
and
MT = mural trophoblast,
H = hypoblast. There is no net growth over this period
and so cells serially decrease in size (“cleavage” divisions) and
the embryo remains approximately the same total size until blastocoelic fluid
formation (102). The baseline (green) represents the approximate typical time
course of events in hours elapsed since fertilisation. Throughout, microvillous
cortex is shown in thick red and non-microvillous adhesive membrane in thin red.
Fertilisation to give the zygote is marked by the sperm entry site and the transient
fertilisation cone (S) of an oocyte, which has an axis (dashed line) from the
animal (A) pole (1st polar body/2nd meiotic spindle) to the vegetal (V) pole.
The first cleavage division is meridional, approximately along the A-V axis in
most zygotes. Two waves of zygotic gene activation (transcription; ZGA) occur,
producing a minor population of mRNAs at ZGA1 and a major population at ZGA2,
at which time most maternal mRNA is degraded, although maternal proteins persist
into the blastocyst stage. During the 8-cell stage, individual cells polarise
(note restriction of microvilli to apical surface), maximise intercellular contact
(compaction) and initiate junctional formation. Note that some polarised 8-cells
(*) are more superficially located than others. These divide conservatively to
generate two outer polar cells at the 16-cell stage, whereas the less superficial
8-cells divide to give one outer polar and one inner non-polar cell (in the illustrated
embryo yielding 6 inner and 10 outer cells). After a further round of cell divisions
to the 32-cell stage (not all cells shown), formation of the nascent blastocoel
(NB) occurs and the inner cells (purple) are separated from the nascent blastocoel
by trophoblastic processes. With full expansion of the blastocoel (B), division
to the 64-cell stage has already commenced and two committed tissue lineages
are now present: inner pluriblast (P, purple) and outer trophoblast, which is
designated mural (MT) adjacent to blastocoel and polar (PT) over the pluriblastic
cells that make up the inner cell mass (ICM). Over the next 12-24 hours the embryo’s
cells continue to increase in number, the blastocoel expands further, the trophoblastic
processes overlying the ICM withdraw, and a layer of hypoblast (H) cells derived
from the pluriblast cells is evident on the surface of the ICM. The remaining
cells of the ICM are now called epiblast (E). The embryo sheds its outer acellular
coating (the zona pellucida – not shown) and initiates attachment to the
uterine epithelium. |
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My current research interests straddle science, law,
and the history of medicine. In the laboratory, in conjunction with
MB PhD student Catherine Aiken (cema2@cam.ac.uk), we are exploring
mitochondrial DNA replication during mouse development and the impact
of maternal diet on it. I also work with Magda Zernicka-Goetz (mzg@mole.bio.cam.ac.uk,
a member of this Department based in the Gurdon Institute) and her
group investigating the cellular and molecular mechanisms underlying
cell allocation and commitment in the early mouse embryo.
I am exploring the ethico-legal issues raised by modern reproductive
technologies and their social and political impact. My most recent
work was initiated early in 2006 when I held a Visiting Fellowship
at Centre for Advanced Study at La Trobe University, Melbourne. Part
of this work is being continued in conjunction with Professor Kerry
Petersen (K.Petersen@latrobe.edu.au).
Historical research into the study of mammalian development and its
influences on both the science and legislative regulation of human
embryo research is being initiated with Professor Sarah Franklin (S.Franklin@lse.ac.uk,
LSE) and Nick Hopwood (ndh12@cam.ac.uk, Cambridge).
I am also co-editing the proceedings of the fifth seminar of the Cambridge
Socio-legal Group called Death Rites and Rights to be published by
Hart Publishing in 2007. Finally, I am preparing the 6th Edition of
Essential Reproduction (Blackwell Science) due out in 2007.
Selected recent publications
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