Chapter 15- Lateral mesoderm and endoderm Recall lineages Fig Fig mesoderm lineages Intermediate Kidney, gonads Paraxial HeadSomite Cartilage, skeletal, dermis Lateral Circulatory, Body cavity, extraembryonic Notochord Fig mesoderm lineages Somatic mesoderm Splanchnic mesoderm Coelom -becomes the body cavity -becomes body cavity wall and the the heart -becomes body cavity wall

How does the heart develop?? 1. Splanchnic mesoderm halves begin to merge 2. These cells differentiate into endocardium (heart lining and valve precursors and myocardium (heart muscles) 25hr26hr Endocardium 3. Endocardium tubes fuse 4. Mycocardium fuses Fig hr 28hr 5. Heart begins beating even while fusion is occurring 72hr Myocardium Lateral mesoderm

Blood vessel formation Note: Blood vessels form independently of the heart, then link up Constraints on blood vessel construction 1.Physiological- an organism must: Obtain nourishment before the intestine develops Use oxygen before there are lungs Excrete wastes before there are kidneys 2. Evolutionary- Six pairs of aortic arches loop out- these enable primitive fish gills to oxygenate blood, but these serve no obvious purpose in mammals and birds. 3. Physical- Blood flows easier through large vessels, yet efficient diffusion requires small vessels and slow moving blood Solution- Large vessels branch into very small ones with overall more cumulative volume capacity Fig “extra” archs in mammal development 2 steps- vasculogenesis and angiogenesis Some background Info Lateral mesoderm

1. Vasculogenesis Blood vessels and blood cells are intimately connected Endothelial cells line blood vessels Fig Angiogenic cell cluster (blood islands) Endothelial cellsMesenchyme Primitive blood cells Fig Blood vessel formation BMP Lateral mesoderm

Transcription factors in vasculogenesis 1. FGF2 is required for hemangioblast formation 2. VEGF is required for blood island and blood vessel formation 3. Ang1 is required proper blood vessel formation (involved in communication between endothelial cell and smooth muscle) 1. Vasculogenesis VEGF is a target for tumor therapy “Tumors gotta eat” Lateral mesoderm

2. Angiogenesis Definition- Remodeling and pruning of capillary beds, arteries and veins Note- Capillary networks of each organ arise within the organ itself, not from larger vessels! VEGF plays key role TGF  stabilizes capillary network PDGF recruits pericyte cells to ensure flexibility of capillaries Lateral mesoderm

2. Angiogenesis Arteries vs. veins?? Arteries have EphrinB2 in cell membranes Veins have EphrinB2 receptor (called EphB4) in cell membranes Functions of the EphrinB2/EphB4 system 1.Ensure that arteries only link up with veins, not other arteries 2.Ensure capillary fusion only occurs with like cells (e.g. only arteries with arteries) Arterial (EphrinB2) Venous (EphB4) Fig Lateral mesoderm

2. Angiogenesis Many organs make their own angiogenesis factors Example- placenta Developing placenta secretes proliferin to promote angiogenesis, then later secretes proliferin-related protein to inhibit angiogenesis Angiogenesis plays key role in tumor development A tumor must induce vascularization in order to enlarge Hence, if use a drug that inhibits this angiogenesis, can possibly slow cure some cancers Lateral mesoderm

Development of Blood Cells Stem cells – embryonic cells capable of producing many cell types, including other stem cells Largest population of stem cells is in the bone marrow Fig Stem Cell (CFU-M,L) “Committed”“Differentiating”“Differentiated” B-cell lineage T-cell lineage Lateral mesoderm

Development of Blood Cells Fig Stem Cell (CFU-M,L) “Committed”“Differentiating”“Differentiated” B-cell lineage T-cell lineage The stem cell (CFU-M,L) also gives rise to another cell lineage Myeloid precursor cell Red blood cells Platelets Basophils Eosinophils Neutrophils Macrophage Note that this is the point of no return- cells are committed to a becoming only one cell type Paracrine factors that direct blood cell formation are termed “cytokines” Lateral mesoderm

Development of Blood Cells Blood development (hematopoiesis) occurs in two phases 1. Embryonic Occurs in blood islands in mesoderm near the yolk (recall fig ) Angiogenic cell cluster (blood islands) Fig Supplies developing embryo with oxygen BMP2 and 4 inhibit blood and blood vessel formation Transitory- disappear later in development 2. Definitive Formed in nodes of mesoderm surrounding aorta (in a region called the aorta-gonad-mesonephros (AGM) region) Lasts the lifetime of the individual Example- In mouse, stem cells originate in yolk sac, then later in AGM region Fig Lateral mesoderm

Endoderm Embryonic endoderm gives rise two tubes Digestive tube (Esophagus,stomach,small intestine,colon) Respiratory tube Buds into Liver, gallbladder, pancreas Lungs Primitive gut Endoderm Fig Pharyngeal arches Auditory cavities Tonsil walls Thymus (T-cell development) Parathyroid Lungs (sprout form base of forth arch) Recall Fig Anterior endoderm – tissues are derived from pharyngeal arches

2. Posterior endoderm The hepatic diverticulum buds out form the foregut, then branches to form liver, pancreas and gall bladder StomachLiver bud Gall Bladder Pancreas (ventral) The pancreas is actually formed by the fusion of two distinct buds (one ventral and one dorsal) Pancreas (dorsal) Fig

Fig The cardiac mesoderm secretes FGF that blocks the factors that inhibit liver induction The notochord (and mesenchyme) produces factors that prevent liver induction What directs formation of liver from the endoderm?? Thus, FGF signals the proximal region of the endoderm to become liver

The respiratory tube Lungs are one of the last organs to differentiate Alveolar cells of the lung produce surfactant at 34 weeks gestation Thus, a premature infant cannot breathe properly Fig foregut Lung buds Pharynx trachea esophagus Week 4 (humans)

Four problems of a land-dwelling egg 1. Desiccation SolutionProblem Amnion secretes amnionic fluid into embryo 2. Gas Exchange 4. Waste disposal- 3. Nutrition Chorion exchanges gases Allantois holds waste (vestigal in humans) Yolk duct supplies nutrients from blood vessels in yolk Day 2 chick embryo Day 9 chick embryo Fig