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Home >Alex Lab

Fertilization, meiotic cell cycle control and development
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Alex McDougall (CR1 CNRS ATIPE)

Fertilization has been studied in Villefranche Marine Station since the days of Fol (1886-91). Although we have moved on a little since that time, it is remarkable that we still do not know how the sperm causes egg activation in any invertebrate at the moment of fertilization. Since ascidians are the closest extant invertebrate relative of the vertebrates we use these marine invertebrate chrodates to study the mechanism of fertilization.

We also work on maternal homologous chromosome segregation.  This process is error prone in humans and is the leading cause of trisomy (Down's syndrome) and reduced fertility as women approach the menopause. Almost all of the autosomal aneuploidies described  in human oocytes occurs at the first meiotic division (metaphase I - anaphase I transition). Here ascidians are useful because their unfertilized eggs are arrested at metaphase I  and they produce vast numbers of eggs (up to 1/2 ml per animal) making them useful for proteomic analysis.

Our other interest is how the cell cycle machinery is controlled during development. The speed of cell division in ascidian embryos starts to decrease at the 16 cell stage. This asynchrony in the rate of cell division is maintained after gastrulation and further amplified when some cells stop dividing at the tailbud stage such as the muscle and notochord lineages whilst others such as the endoderm continue to divide. The net result of this is that a tadpole larva composed of ~2600 cells is produced containing precisely 36 muscle cells, 40 notochord cells, 330 central nervous system cells, about 500 endoderm cells and a large number of epithelial cells.

(see Fertilization BioClip and Meiosis BioClip)

Sparks of lifeTwisted sisters


Dernière mise à jour : 30 juillet 2010

Download Meiosis Bioclip    

Our three research interests
Fertilization Contraction Development

The first calcium increase (image 1) at fertilization triggers a visible contraction (2) of the egg culminating in the formation of a surface protrusion termed the contraction pole that acts as a calcium wave pacemaker.  The unfertilized egg is arrested in metaphase I (3, metaphase I spindle) making it convenient to study the metaphase I-anaphase I transition.  Approximately 12-15 hours after fertilization a tadpole larva begins to form (4, the green colour is EGFP fluorescence). 

We use the oocytes from these primitive marine chordates (Ascidians or sea squirts) in the study of fertilization, meiosis and early development.


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People in the lab

Alex McDougall  (CR1)
Remi Dumollard (CR1)
Karen Lee WING MAN
Celine Hebras (Technician)

Contact details 
BIODEV, UMR7009, Station Zoologique, Villefranche-sur-Mer 06230, FRANCE.

Previous lab members

Michael Carroll (former PhD student) 

Hayden Homer (former PhD student) 

Jean-Phillipe Chambon (former postdoctoral researcher) 

Francois Prodon (former postdoctoral researcher) 

Alexandre Paix (former postdoctoral researcher) 

 ll@obs-vlfr

Clinical Embryologist, Manchester , UK

Clinical Lecturer UCL, UK 

Lecturer, University Paris 06, France 

Research Engineer, University of Nice-Sophia Antipolis 

Postdoctoral Researcher John Hopkins (Sedoux lab)
Collaborators  

Keith T Jones/Antony J O'Sullivan

K.T.Jones@ncl.ac.uk
A.J.OSullivan@durham.ac.uk

Mary Herbert

mary.herbert@newcastle.ac.uk

Mark Levasseur

m.d.levasseur@ncl.ac.uk
Current funding

CNRS ATIPE
ARC
ANR

 http://www.cnrs.fr/SDV/Atip/atipintro.html         

Selected Recent Publication

Dumollard ,R., Levasseur ,M., Hebras, C., Huitorel, P., Carroll, M., Chambon, J-P. and McDougall,. A. (2011).  Mos limits the number of meiotic divisions in urochordate eggs. Development, 138. 885-895.

Prodon, F., Chenevert, J., Hébras, C., Dumollard, R.,  Faure, E., Gonzalez-Garcia,F.,  Nishida, H., Sardet, C and McDougall, A. (2010). Dual mechanism controls asymmetric spindle position in ascidian germ cell precursors. Development, 137, 211-221.

Chambon, J.P., Nakayama, A., Takamura, K., McDougall, A, and Satoh N. (2007). ERK- and JNK-signalling regulate gene networks that stimulate metamorphosis and apoptosis in tail tissues of ascidian tadpoles. Development 134 1203-1209

Levasseur, M., Carroll, M. Jones, K. T. and McDougall, A. (2007). A novel mechanism controls the Ca2+ oscillations triggered by activation of ascidian eggs and has an absolute requirement for CDK1 activity. J. Cell Sci. 120 1763-1777

Sardet, C, Dumollard, R, McDougall, A. (2006). Signals and calcium waves at fertilization. Semin Cell Dev Biol 17 223

Homer, H. A., McDougall,A., Levasseur, M. and Herbert, M. (2005). Restaging the spindle assembly checkpoint in female mammalian meiosis I. Cell Cycle 4 1-5

Homer, H.A., McDougall, A., Levasseur, M., Murdoch, A.P and Herbert, M. (2005). Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes. Reproduction 130 829-843

Homer H.A., McDougall A., Levasseur M., Murdoch, A and Herbert, M. (2005). RNA iterference in human oocytes: towards an understanding of human aneuploidy. Mol Hum Reprod 11 397

Parry, H., McDougall, A. and Whitaker, M. Microdomains bounded by endoplasmic reticulum segregate cell cycle calcium transients in syncytial Drosophila embryos. J. Cell Biol. 171 47-59

McDougall, A., Elliott, D. J. and Hunter, N. (2005). Connecting, pairing,exchanging, pausing and pulling chromosomes. EMBO Reports, 6, 120-125
Homer, H. A., McDougall, A., Levasseur, M.,Yallop, K., Murdoch, A. P. and Herbert, M.  (2005). Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes. Genes Dev. 19, 202-207

Herbert,M., Levasseur, M., Homer, H., Yallop, K., Murdoch, A and McDougall, A. (2003). Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin. Nat. Cell Biol. 5 1023-1025. 5, 1023-1025.

Levasseur, M and McDougall, A. (2003). IP3 responsiveness is regulated in a meiotic cell cycle dependent manner: implications for fertilisation induced calcium signaling. Cell Cycle 2(6): 610-614.

Carroll, M., Levasseur, M., Wood, C., Whitaker, M., Jones, K. T, and McDougall A.(2003). Exploring the mechanism of action of the sperm-triggered calcium wave pacemaker in ascidian zygotes. J. Cell Sci. 116, 4997-5004.

Nixon, V. L., Levasseur, M., McDougall, A. and Jones, K. T. (2002). Calcium oscillations promote APC/C-dependent cyclin B1 degradation during metaphase arrest and completion of meiosis in fertilizing mouse eggs. Current Biol. 12, 746-750.

McDougall, A., Levasseur, M., O`Sullivan, A. J. and Jones, K. T. (2000). Cell cycle-dependent repetitive Ca2+ waves induced by a cytosolic sperm extract in mature ascidian eggs mimic those observed at fertilization.  J. Cell Sci. 113, 3453-3412.

Levasseur, L. and McDougall, A. (2000). Sperm-induced calcium oscillations at fertilisation in ascidians are controlled by cyclin B1-dependent kinase activity. Development 127, 631-641.

 

 


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