The Pennsylvania State University ©1997

DEPARTMENT OF VETERINARY SCIENCE

VSC/BMMB 519 - 

Development of the Hematopoietic and Vascular System

Thursdays  2:30-4:25 Room 9 Henning Building                     2 Credits

 

Instructor: Robert Paulson  Office 104 Henning 

                            Phone 863-6306

                            email rfp5@psu.edu

 

Format: During each class we will analyze two to three papers from the primary literature. Students will present the papers and the class will discuss the each paper. The emphasis of the course will be on understanding the techniques used and how the results of the paper fit into the broader context of Developmental biology.

 

Grading: Each student will be graded on their presentations and their participation in class.

 

Syllabus:

 

August

23

Introduction to hematopoiesis, mouse, frog and fish development. (Bob Paulson).

 

30

Mesoderm formation in mice: Role of the Ectoderm in patterning The mesoderm.

September

6

Patterning the mesoderm in Frogs: Factors that induce mesoderm and Fate mapping hematopoietic tissue.

 

13

Origins of hematopoietic and endothelial cells in Zebrafish: a genetic approach.

 

20

Hemangioblasts-bipotential progenitors of hematopoietic and endothelial cells.

 

27

Flk-1 and Sci markers for hemangioblast.

October 

4

Using ES cells to study hemangioblast development I I   The origin of Primitive and definitive progenitors

 

18

The origin of hematopoietic stem cells in the embryo

 

25

The role of the yolk sac in definitive hematopoiesis  

November

1

Runx1 and the development of definitive hematopoiesis in the fetal    liver

 

8

Adhesion molecules and the homing of stem cells to the fetal liver and bone marrow

 

15

Role of receptor tyrosine kinases in vasculogenesis

 

22

Thanksgiving

 

29

Angiogenesis and the remodeling of the vasculature.

December

6

The role of oxygen in the development of the hematopoietic and vascular system.

 

 

August 23

Introduction to hematopoiesis, mouse, frog and fish development.(Bob Paulson)

 

August 30

Mesoderm formation in mice- Role of the Ectoderm in patterning the mesoderm.

 

Hematopoictic induction and respecification of A-P identity by visceral endoderm signaling in the mouse embryo. M. Belaoussoff et al. Development 125:5009-5019 (1998).

 

Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. Dyer MA, Farrington SM, Mohn D, Munday M Baron ME. Development. (2001) 128:1717-1730.

 

September 6

Patterning the mesoderm in Frogs: Factors that induce mesoderm and Fate mapping hematopoietic tissue.

 

The origins of primitive blood in Xenopus: implications for axial patterning. MC Lane and WC Smith (1999) Development 128:423-434.

 

Bipotential primitive-definitive hematopoietic progenitors in the vertebrate embryo. J Turpen, C Kelley, P Mead and L Zon. Immunity (1997) 7:325-334.

 

The role of BNV-4 and GATA-2 in the induction and differentiation of hematopoietic mesoderm in Xenopus laevis. Maeno M, Mead PE, Kelley C, Xu RH, Kung HF, Suzuki A, Ueno N, Zon LI. Blood. (1996) 88:1965-1972.

 

September 13 

Origin of hematopoietic cells and endothelial cells in Zebrafish. 

Cloche, an early acting zebrafish gene, is required by both the endothelial and hematopoietic lineages. D Stanier et al. Development (1995) 121:3141-3150.

 

Cell-autonomous and non-autonomous requirements for the zebraffsh gene cloche in hematopoiesis. Parker L, Stainier DY. Development. (I 999) 126:2643 -5 1.

 

The Scl gene specifies haemangioblast development from early mesoderm. M Gering et al. EMBO Journal (1998) 17:4029-4045.

 

September 20 

Hemangioblasts-bipotential progenitors of hematopoietic and endothelial cells: evidence from avian embryos.

 

Two distinct endothelial lineages in ontogeny, one of them related to hemopoiesis. Pardanaud L, Luton D, Prigent M, Bourcheix LM, Catala M, Dieterlen-Lievre F. Development. (1996) 122:1363-1371.

 

Manipulation of the angiopoietic/hemangiopoietic commitment in the avian embryo, Pardanaud L, Dieterlen-Lievre F. Development. (1999) 126:617-627.

 

Tracing the progeny of the aortic hemangioblast in the avian embryo. T Jaffredo et al. Developmental Biology (2000) 224:204-214.

 

 

September 27 

Flk-I and Sel: markers for the hemangioblast. Failureofblood-islandformationandvasculogenesisinFIk-l-deficientmice. ShalabyF, Rossant J, Yamaguchi TP, Gertsenstein M, Wu X:F, Breitman ML, Schuh AC. Nature. (1995) 376:62-66.

 

A requirement for Flkl in primitive and definitive hematopoiesis and vasculogenesis Shalaby F, Ho J, Stanford WL, Fischer KD, Schuh AC, Schwartz L, Bernstein A, Rossant J. Cell. (1997) 89:981-90.

 

SCL specifies hematopoietic mesoderm in Xenopus embryos. Development. Mead PE, Kelley CM, Hahn PS, Piedad 0, Zon LI. (1998) 125:2611-2620.

 

Unsuspected role for the T-cell leukemia protein SCL/tal- I in vascular development. Visvader JE, Fujiwara Y, Orkin SH. Genes Dev. 1998 Feb 15; 12(4):473 -9.

 

October 4

Using ES cells to study hemangioblast development

 

A Common Precursor for hematopoietic and endothelial cells. K Choi et al. Developemnt (1998) 125:725-732.

 

Basic fibroblast growth factor positively regulates hematopoietic development. P Faloon et al. Development (2000) 127:1931-1941.

 

A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor Scl/tal-1. SM Robertson et al. Development (2000) 127:2447-2459.

 

Regulation of hemangioblast development. Lacaud G. et al. Annal of the NY Academy of Science (2001) 938:96-107. Review

 

October 11   

The origin of Primitive and definitive progenitors

 

Properties of the earliest clonogenic hemopoietic precursors to appear in the developing murine yolk sac. Wong PM, Chung SW, Chui DH, Eaves CJ. Proc Nati Acad Sci U S A. (1986) 83:3851-3854.

 

Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Palis J, Robertson S, Kennedy M, Wall C, Keller G Development. (1999) 126:5073-5084.

 

In vitro development of primitive and definitive erythrocytes from different precursors. T Nakano, et al. Science (1996) 272:722-724.

 

A common precursor for primitive erythropoiesis and definitive haematopoiesis.

 

Kennedy M, Firpo M, Choi K, Wall C, Robertson S, Kabrun N, Keller G. Nature. (I 997) 386:488-493. 

Yolk-sac hematopoicsis. The first blood cells of mouse and man. Palis J, Yoder MC. Exp Hematol. (2001) 29:927-936. Review

 

October 18  

The origin of hematopoietic stem cells in the embryo

 

An early pre-liver intraembryonic source of CFU-S in the developing mouse. Medvinsky AL, Samoylina NL, Muller AM, Dzierzak EA Nature. (I 993) 3 64:64-67.

 

Definitive hematopoiesis is autonomously initiated by the AGM region. Medvinsky A, Dzierzak E. Cell. (I 996) 86:897-906.

 

Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo. Sanchez MJ, Holmes A, Miles C, Dzierzak E. Immunity. (1996) 5:513-25.

 

October 25      

The role of the yolk sac in definitive hematopoiesis

 

Characterization of definitive lymphohematopietic stem cells in the day 9 murine yolk sac. M Yoder, et al. Immunity (1997) 7: 335-344.

 

Spatial and temporal emergence of high proliferative potential hematopoietic precursors during murine embryogenesis. J Palis, et al. PNAS (2001) 98:4528-4533.

Generation of definitive hematopoietic stem cells from murine early yolk sac and paraaortic splanchnopleures by aorta-gonad-mesonephros region-derived stromal cells. Sahoko Matsuoka, et al. Blood (2001) 98: 6-12.

 

Introduction: spatial origin of murine hematopoietic stem cells. M Yoder Blood (2001) 98: 3-5. Review

 

November 1

Runxl and the development of definitive hematopoiesis in the fetal Liver.

 

Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. North T, Gu TL, Stacy T, Wang Q, Howard L, Binder M, Marin-Padilia M, Speck NA Development. (1999) 126:2563-2575.

 

Haploinsufficiency of ANILI affects the temporal and spatial generation of hematopoietic stem cells in the mouse embryo. Cai Z, de Bruijn M, Ma X, Dortland B, Luteijn T, Downing RJ, Dzierzak E. Immunity. (2000) 13:423-43 1.

 

The AUL I transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region. Y Mukouyama et al. Developmental Biology (2000) 220:27-36.

Potential roles for RUNX I and its orthologs in determining hematopoietic cell fate. Tracey V;]D, Speck NA. Sen@n Cell Dev Biol. (2000) 11:337-342. Review

 

November 8 

Adhesion molecules and the homing of stem cells to the fetal liver and bone marrow

 

Impaired migration but not differentiation of hematopoietic stem cells in the absence of DI integrins. E Mrsch, et al. Nature (1996) 380:171-175.

 

Fetal and adult hematopoietic stem cells require 0 1 integrin function for colonizing fetal liver, spleen and bone marrow. A Potocnik, et al. Immunity (2000) 12:653-663.

 

(x4 integrins regulate the proliferation/differentiation balance of multilineage hematopoietic progenitors in vivo. A Arroyo, et al. Immunity (1999) 11:555-566.

 

November 15 Role of receptor tyrosine kinases in vasculogenesis

 

Flkl positive cells derived from embryonic stem cells serve as vascular progenitors. J Yamashita, et al. Nature (2000) 408:92-96.

 

Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development. Puri MC, Partanen J, Rossant J, Bernstein A. Development. (I 999) 126:4569-4580

 

Abnormal blood vessel development and lethality in embryos lacking a single VF-GF aliele. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Nature. (1996) 380:435-439.

 

Vasculogenesis in the mouse day 6.5 to 9.5 embryo. C Drake et al., Blood (2000) 95:1671-1679.

 

November 22 

Thanksgiving

 

November 29 

Angiogenesis and the remodeling of the vasculature.

 

Requisite role of angiopoietin- 1, a ligand for the TIE2 receptor, during embryonic

 

angiogenesis. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Cell. (1996) 87:1171-1180.

 

Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Hellstrom M, Kal n M, Lindahl P, Abramsson A, Betsholtz C. Development. (1999) 126:3047-3055.

 

December 6 

The role of oxygen in the development of the hematopoietic and vascular system.

 

A developmental transition in definitive erythropoiesis: erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4. Takako Makita, Gabriela Hemandez-Hoyos, Tim Hung-Po Chen, Hong Wu, Ellen V. Rothenberg, and Henry M. Sucov. Genes Dev. (2001) 15: 889-901.

 

Multilineage embryonic hematopoiesis requires hypoxic ARNT activity. David M. Adelman, Emin Maltepe, and M. Celeste Simon Genes Dev. (1999) 13: 2478-2483.