Developmental biology: a brief introduction to development, and to the use of animal model systems

1. Stem Cell Research and Developmental BiologyMRC Centre for Developmental and Biomedical GeneticsandDept of Biomedical Science

2. Developmental biology: a brief introduction to development, and to the use of animal model systems Impact of developmental biology on Stem Cell Research: Derivation, Differentiation and Identification of ‘es cells’ Definition of other types of ‘stem cell’ Animal models as test-beds for transplantation

3. Developmental Biologists: use animal models to understand how we develop into a functional organism. A key aim: to identify particular cell types and elucidate the cellular and molecular pathways that regulate organ and tissue formation

4. Muscle cell differentiation/ Musculoskeletal disease: Tools available that define discrete cell types (shown by the different colours) Neuronal differentiation Neurodegenerative diseases

5. Modelling arteriogenesis using the zebrafish Ingham/Chico/Crossman Tools increasingly sophisticated: allow imaging of discrete cells in real time in vivo

6. Can use animal models: development conserved (tissue and cell types; pathways that define discrete cell types)

8. Key aim: to understand the balance between cell division and differentiation

9. tissue allocation self renewal gastrulation cleavage differentiation totipotent pluripotent committed multipotent 1. Detailed understanding of the specification and differentiation of cellular systems (neuronal, musculoskeletal, vascular) 2. Balance between proliferation (self renewal) and differentiation

10. Developmental biology: a brief introduction to development, and to the use of animal model systems Impact of developmental biology on Stem Cell Research: Derivation, Differentiation and Identification of ‘es cells’ Definition of other types of ‘stem cell’ Animal models as test-beds for transplantation

12. Inner cell mass: origin of ‘es cells’

13. Es cells: in vitro can self-renew indefinitely, or differentiate to many fates

14. Impacts of developmental biology: • Characterisation of inner cell mass and es cells • Understanding of cell types present (using ‘markers’) • Understanding of pathways that regulate self-renewal • and differentiation

15. Points to note: No single marker exists that defines a stem cell Proliferating es cells in vitro are an artefact: in vivo, cells of the inner cell mass will go on to finely balance proliferation and differentiation, to build an organism Mouse and human es cells: key differences

16. Derivation, Differentiation and Identification of ‘es cells’ • Definition of other types of ‘stem cell’ Emerged from studies of haematopoeisis (initially) and more recently through developmental biology studies that analyse the origins of tissue and organ progenitors

17. Haematopoetic system: original definition of stem cell: indefinite self-renewal; complete cellular reconstitution

20. Other sites where renewal necessary into adulthood include: Skin Gut Muscle Clear signs of new cell production in adults in other regions including: Brain Question: are there ‘stem cells’ present in these locations? Defining experiments have not been performed

21. Some questions: Can regeneration occur in the absence of ‘stem cells’ (self-renewing, multi-potent cells)?

22. Can we identify adult ‘stem cells’ ?

23. 4 factors (Yamanaka; 2006, 2007)

24. Portfolio of activities • Description of stem cells • Description of self-renewal versus differentiation pathways • Directed differentiation of stem cells.

25. And finally….. • Tests for integrity and function of es-derived cells