Molecular Embryology

Lead Research Organisation: MRC London Institute of Medical Sciences

Abstract

During embryonic development cells go from a naove state to a differentiated state where they form the different tissues and organs of the body. For a cell to know the precise organ it is going to give rise to it needs to acquire information, one of the first steps that occurs during development is the establishment of a body plan that provides the basis of this information. This body plan allows the cells of the embryo to know exactly where they are and therefore what organ to give rise to. The first step in the development of this body plan is to determine the three definitive axes of the embryo: anterior-posterior (head to feet), dorso-ventral (back to front) and left-right. These will give the coordinates that the cell will read and then use to become a specific cell type. Therefore to understand how each cell type works, or why it stops working in disease, it is essential to understand first how the embryonic axis are established.||We are studying how the first of these axes to be determined (the anterior-posterior axis) is established in the mouse embryo. A critical event in the development of the anterior-posterior axis is the induction and asymmetric movement of a small group of cells that are required for the head to form. Where these cells move to in the embryo will determine where the head will be. The role of these cells in head formation is to instruct the cells around them to form the head region of the embryo. We study how these cells are induced, what directs the movement of these cells and finally we investigate how these cells tell those cells around them to become the head of the embryo. We use the mouse as our model system given that its early development is very similar to the development of the human embryo. Furthermore, in mouse we can manipulate single genes making it possible to determine what the function of the genes are and what role they play in anterior-posterior axis formation.

Technical Summary

Our main focus is to understand the molecular and cellular events that pattern the early mammalian embryo. In particular we are studying the signalling pathways and cell movement events that are important for anterior-posterior axis development. Our lab takes two approaches. The first approach is to study the function of the anterior visceral endoderm (AVE), an extra-embryonic signalling centre required for neural induction and therefore critical for anterior-posterior axis development. Our work focuses on understanding how the AVE is induced, what are the cellular and molecular cues for the cell movements the AVE undergoes, and finally, how does the AVE pattern the embryo proper. The second approach is to understand the signals that induce neural identity in the early mouse embryo. We aim to identify the molecules that drive the naove and undifferentiated cells of the early embryo to a neural fate. With both approaches our aim is to understand how the patterning activities of signalling centres, cell movement events and proliferation and cell survival signals are integrated during the morphogenesis of the embryo. We use the mouse as a model of mammalian development due to the availability of genetics that this organism offers. We analyse loss and gain of function mutations so as to identify the molecular pathways that control development.||It has become clear that genetic pathways responsible for orchestrating early embryonic development are remarkably conserved amongst vertebrate species. Although first active during embryogenesis many of these pathways are used again in the adult, especially during processes involving tissue renewal. Consequently, the genetic analysis of development in the mouse has direct relevance to the molecular basis of congenital abnormalities and other pathological conditions, such as neoplasia and defective tissue repair, in humans.

Publications

10 25 50

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Crompton LA (2007) Early embryonic expression patterns of the mouse Flamingo and Prickle orthologues. in Developmental dynamics : an official publication of the American Association of Anatomists

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Di-Gregorio A (2007) BMP signalling inhibits premature neural differentiation in the mouse embryo. in Development (Cambridge, England)

 
Description EMBO Fellowship (MicroRNAs involvement in mouse trophoblast development)
Amount £7,500 (GBP)
Organisation European Molecular Biology Organisation 
Sector Charity/Non Profit
Country Germany
Start 01/2007 
End 12/2007
 
Description Fellowship - Spanish Government
Amount £3,100 (GBP)
Organisation Spanish Ministry of Science and Innovation 
Sector Private
Country Spain
Start 01/2008 
End 12/2008
 
Description Fellowship - Spanish Government
Amount £1,800 (GBP)
Organisation Spanish Ministry of Science and Innovation 
Sector Private
Country Spain
Start 01/2006 
End 12/2006
 
Description Lister Research Prize Fellowship (The role of the anterior visceral endoderm in establishing the anterior-posterior axis of the mouse embryo)
Amount £257,956 (GBP)
Organisation Lister Institute of Preventive Medicine 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2006 
End 09/2008
 
Description Studentship: Function of Bmpr1a in ES cells differentiation and cell competition
Amount £100,000 (GBP)
Organisation New University of Lisbon 
Department Foundation for Science and Technology
Sector Academic/University
Country Portugal
Start 11/2006 
End 10/2009
 
Description External Collaborators 
Organisation National Center for Cardiovascular Research (CNIC)
Country Spain 
Sector Academic/University 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
 
Description External Collaborators 
Organisation National Institutes of Health (NIH)
Country United States 
Sector Public 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
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Description External Collaborators 
Organisation Osaka University
Country Japan 
Sector Academic/University 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
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Description External Collaborators 
Organisation University College London
Department Biosciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
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Description External Collaborators 
Organisation University of Lisbon
Department Institute for Molecular Medicine
Country Portugal 
Sector Academic/University 
PI Contribution Exchange of ideas, reagents and joint publications
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Description External Collaborators 
Organisation University of Oxford
Department Department of Biochemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
 
Description External Collaborators 
Organisation University of Oxford
Department Department of Physiology, Anatomy and Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
 
Description Internal Collaborators 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
Start Year 2007
 
Description Internal Collaborators 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
Start Year 2007
 
Description Internal Collaborators 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
Start Year 2007
 
Description Internal Collaborators 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Exchange of ideas, reagents and joint publications
Collaborator Contribution Exchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publicationsExchange of ideas, reagents and joint publications
Impact Joint publications
Start Year 2007