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Organogenesis

Module: 
4
Section: 
B

Instructor: Brigid Hogan
Summary: Many organs of the body – for example the kidney, pancreas, lungs, ear and limbs – are composed of epithelial and mesenchymal cell populations organized into complex three-dimensional tissues with a dedicated blood and nerve supply. How are these adult organs built during development? They originate in the embryo from small collections of cells known as “primordia” that contain progenitors that will give rise to all the different mature epithelial and mesenchymal cell types. In order to understand how the process of organ development - or organogenesis - is controlled we must address many important questions. For example, we need to know how the epithelial and mesenchymal populations communicate with each other so that their proliferation and differentiation are co-ordinated, how they acquire specific 3D shapes specific to each organ and its physiological function, how blood vessels, nerves and lymphatics develop alongside the epithelial and mesenchymal components, and how adult stem cells are sequestered within the adult organ and maintain it throughout life. Answering these questions is important for many reasons: defects in organogenesis underlie many congenital abnormalities; understanding how organs develop in vivo can help us to bioengineer replacement tissues from embryonic stem cells in the lab; deciphering how different cell types cross talk during development can provide clues to processes such as tumor-stromal interactions, wound repair and aging.
In this module we will read and discuss primary research papers relevant to core processes common to the development of many organ systems: (1) Branching morphogenesis – the process by which a simple bud of epithelial and mesenchymal cells gives rise to a branched, tree-like structure with region-specific differentiation of cell types; (2) Self organization of tissues in 3D organoid cultures; (3) Tissue vascularization and innervation during development; and (4) making stem cell niches.

Readings: 

1) Guillot, C., and Lecuit, T. (2013) Mechanics of epithelial tissue homeostasis and morphogenesis. Science 340: 1185-1189
2) Lancaster, M.A. and Knoblich, J.A. (2014) Organogenesis in a dish: Modeling development and disease using organoid technologies Science 345: DOI: 10.1126/science.1247125
3) Hatch, J and Mukouyama Y.S. (2015) Spatiotemporal mapping of vascularization and innervation in the fetal murine intestine Dev Dyn 244: 56-68
4) Udan, R.S., Culver, J.C. and Dickinson, M.E. (2012) Understanding vascular development Wiley Interdiscip. Rev. Dev Biol. 2
5) Etzrodt, M., Endele, M. and Schroeder, T. (2014) Quantitative single-cell approaches to stem cell research Cell Stem cell 15: 546-58

Optional extra:
1) Keller, P.J. (2013) Imaging morphogenesis: technological advances and biological insights, Science 340, 1234168 DOI: 10.1126/science.1234168
2) Costantini, F. (2012) Genetic controls and cellular behavior in branching morphogenesis of the renal collecting system Wiley Interdiscip. Rev. Dev. Biol. 5: 693-713
3) Heisenberg, C-P., and Bellaiche, Y. (2013) Forces in tissue morphogenesis and Patterning (2013) Cell 153: 948-962