1. Circulatory System Gilbert: Chapter 14, 17

2. Fetal vs. Newborn Circulation (mammals) Must be specialized depending on whether oxygen comes from placenta or from lungs –Specialized fetal hemoglobin (higher affinity for oxygen than mother’s) This is switched to the adult form after birth

4. –Blood does not get oxygen from pulmonary artery Ductus arteriosus: Diverts blood flow from pulmonary artery to aorta and out to placenta Foramen ovale: opening in septum of heart allowing blood to flow from right atrium to left atrium, then left ventricle (skip pulmonary bypass) At birth, this opening closes upon first breath

7. Blood Vessel Formation Form independently and link up with heart –Origins in the Lateral Plate Mesoderm Chance plays important role –Each circulatory system unique –Cannot completely attribute formation of pattern of vessels to genetics Within a species, circulatory systems are similar –Because of constraints upon blood vessel formation

8. Constraints of Blood Vessel Development Physiological –Cells must have nutrients, oxygen obtained from EEM’s –Must develop so that they connect with EEM’s Evolutionary –Conserved patterns even if not needed (ex. Human yolk sac vessels) Physical –Width, volume of vessels are constrained by the efficiency of nutrient transport Wider vessels can transport more blood, but does not have most efficient diffusion

9. 2 methods of Blood Vessel Formation Vasculogenesis –Formation of blood vessels by forming congregates of blood cells (blood islands) and then forming capillaries from them Angiogenesis –Formation of blood vessels by remodeling previously existing vessels –Connects vessels formed by vasculogenesis

10. Blood cells and Blood Vessels Hemangioblasts: pleuripotent stem cells that give rise to both blood cell lineages and blood vessel cells Mutations in transcription factors can delete both blood cells and blood vessels

12. Vasculogenesis Creation of blood vessels de novo from lateral plate mesoderm Cells are specified to become blood islands –HSC’s (hematopoeitic stem cells) form on the inside –Angioblasts form on the outside (precursors to blood vessels) Angioblasts multiply, differentiate into Endothelial cells (lining of blood vessels) Tubes begin to make connections to form capillaries

15. Growth Factors in Vasculogenesis FGF2 (fibroblast growth factor) –Required for making hemangioblasts –What cell types will be affected?? VEGF (vascular endothelial growth factor) –Secreted by mesenchyme cells near blood islands –Enable differentiation of angioblasts, formation of endothelial tubes –HEMANGIOBLASTS/ANGIOBLASTS MUST HAVE RECEPTORS!!

16. Flk1, Flt1 Receptor tyrosine kinases specific for VEGF Mouse models show –Mutants for Flk1 lack yolk sac blood islands –Mutants for Flt1 lack organization of cells into vessels

18. Angiogenesis Secondary formation of vessels –New vessels formed by remodeling, adding on to old vessels, joining vessels together –Can be accomplished by splitting existing vessel in two

20. Angiogenesis in Cancer Metastasis Angiogenesis is also important in tumor formation –Tumor needs nutrients as it grows –Recruits new vessel formation to achieve this Do this by secreting angiogenesis factors Blocking angiogenesis may prevent tumor growth and metastasis (angiostatin, endostatin) –See web site 15.3 from book (www.devbio.com)

21. Blood Cell Development Hematopoeisis –Occurs embryonically and in adult bone marrow (via pleuripotent hematopoeitic stem cells) –Continuous supply of RBC’s, WBC’s all lymphatic and immune cells