Study Questions 7 Flashcards

1
Q
  1. What are somato- and splanchnopleure and which germ layers are involved in their formation?
A

Somatopleure: Parietal serosa. Mesoderm + Ectoderm, relating to the walls – limb bud, dermis
Splanchnopleure: Visceral serosa. Mesoderm + Endoderm, relating to the internal organs, making up the smooth muscle of the gut

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2
Q
  1. What is going to be formed from somatic mesoderm?
A

Limb bud, parietal serosa, dermis of ventral body region, connective tissues of limbs

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3
Q
  1. What is going to be formed from splanchnic mesoderm?
A

Visceral serosa, smooth muscle of gut and respiratory, heart, blood vessles

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4
Q
  1. What are presumptive heart cells? What is cardiogenic mesoderm?
A

Presumptive heart cells
● Undetermined from splanchic mesoderm
● Originate from two patch of epiblast close to anterior primitive streak, proliferate and migrate through streak
● Form two group mesodermal cells at level of Hensen Node in splanchic mesoderm
○ Result in two cardiogenic field on each side body > cardiogenic mesoderm (2 regions of splanchic mesoderm) at each side of body
○ Cardiogenic fields contain presumptive heart cells
Cardiogenic mesoderm – the two cardiogenic fields on each side of body, will combine in an anterior-lateral region relative to the streak, forming the cardiac crescent
● Has precursors of all 3 cells types contributing to endocardium (atrial) and myocardium (ventricular)
○ Differentiate into:
○ Atrial and ventricular myocyte
○ Cushion cells for valves
○ Purkinje conducting fibres (further diff ventricular myocyte)
○ Endothelial lining

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5
Q
  1. What is the role of Wnts and BMPs in the specification of heart precursor cells?
A

BMP – expressed in centre of embryo
● Specify heart precursor cells to become cardiogenic mesoderm and hemangiogenic mesoderm (heart itself) Inhibited by Noggin (From notochord)
● HEART = BMP + WNT INHIBITOR
● anterior endoderm adjacent to the cardiogenic mesoderm induces differentiation of heart through BMP and FGF.
Wnts
● From neural tube
● Induce/promote blood vessel formation in posterior from heart precursors w/ BMP
● Inhibit heart formation in anterior
● Wnt inhibitor of anterior mesoderm prevent Wnt activity in anterior mesoderm so heart formation occurs in anterior
● Wnt inhibitors in anterior mesoderm (whose induction originated from AVE) prevent Wnts from reaching anterior and inhibiting heart formation è Wnt inhibitors inhibit inhibition of hart formation so that we get heart formation in the anterior and blood laterally, posteriorally from heart

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6
Q
  1. What is the role of endoderm in the migration of the cardiac precursor cells? Give one example.
A

● The endoderm controls the direction of movement of presumptive heart cells anterior migration by secreting morphogens to direct the heart’s final location
● Endocardial primordial tubes are brought together by the infolding of the gut (splanchnopleure)
● Myocardial layers are bent toward the midline, enwrapping the endocardial tubes
● Two myocardia form tube (first fusing is at the ventral side). Endocardial primordia also fuse inside the myocardial tube.
● Example – Cardiac Bifida – infolding of gut movement is prevented and mutated endo proteins,
○ Endoderm express “miles apart” protein which directs cardiac precursor cells migration so that they can fuse
■ Mutation result in no movement of cells = no fusion = two hearts formed on each side of body
○ Foxp4 protein that is expressed in endoderm is transcription factor responsible for fusion of two heart primordia

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7
Q
  1. List three factors involved in specification of mesodermal cells into cardioblasts and two factors involved in cardioblasts’ determination into cardiomyocytes. (Take a look at the picture; it’s clearly labeled.)
A
Factors for specification mesodermal --> cardioblast
·   	Wnt
·   	BMP
·   	Fgf
Factors for determination cardioblast --> cardiomyocyte (induce heart-specific proteins)
·   	Nkx2-5
·   	GATA
Mef2 induced by GATA
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8
Q
  1. What is achieved by the looping of the cardiac tube?
A

Looping converts anterior-posterior polarity into right-left polarity which is present in adults. It specifies atria and ventricles, allows atria to remain on top of ventricles
 cells in the central region (yellow) have motile cilia with the motor protein left–right dynein that enables them to set up ciliar motion and produce directed (left –to-right) flow of nodal fluid
 cells which surround centrally positioned cells have non-motile cilia.
• The nodal fluid flow causes the non-motile cilia to bend over - mechanical change, which activates the mechanosensitive Ca2+ channel (protein polycystin-2)
• Ca2+ gradient is formed; higher Ca2+ in the cells on the left side of the node (red cells)
⇒the symmetry-breaking event thought to be responsible for activating the nodal signaling cascade in the left lateral plate mesoderm, causing left-specific expression of some genes, e.g. Lefty and Pitx2
⇒establishment of the left–right axis.

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9
Q
  1. Define hemangioblast, pluripotent HSC and angioblast.
A

Hemangioblast – originate from splanchic mesoderm, common precursor to blood
● Angioblast – endothelial cell precursor, progenitors to blood vessel cells)
Pluripotent hematopoietic stem cell – precursor to blood stem cell and all lineages of blood cells

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10
Q
  1. What is the difference between vasculogenesis and angiogenesis? Where does vasculogenesis occur?
A

Vasculogenesis – creation of primary network of blood vessels from lateral plate mesoderm
· Occur in blood islands (formed by hemangioblasts) of yolk sac (extraembryonic vasculogenesis)
· Occur in blood island of embryo itself (intraembryonic vasculogenesis)
Angiogenesis – remodelling of primary network into capillary bed, arteries, veins, occurs constantly

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11
Q
  1. Describe briefly extraembryonic vasculogenesis.
A

Blood islands form in yolk which form hemangioblast cord to give rise to early red blood cells and vasculature (multipotent cardiac precursors) needed to feed embryo
● Capillary network form (transport nutrients, blood to new heart)
● Outer cells become flat endothelium (line blood vessel)
● Inner cells become primordial blood
○ Differentiation depend on notch (less notch = endothelial cell)
● Extraembryonic process is critical in amniote development. These blood islands eventually produce the vitelline veins and umbilical veins that bring nutrients and respiratory gases to the embryo
● In chick, first blood islands are formed from the cells
● leaving posterior part of primitive streak that form
● extraembryonic mesoderm
● They form cords of hemangioblasts
● In general: outer cells become flat endothelial and line the vessels, the inner cells become primordial blood.
● Eventually form capillary network draining into the vitelline veins (yolk sac) and umbilical veins (placenta in mammals).
● Transport food and blood to the new formed heart.

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12
Q

12.Describe briefly intraembryonic vasculogenesis.

A

● Blood vessels created from beginning of lateral plate mesoderm
● Cords of splanchic mesodermal cells clump along future course of developing vessel
○ Cells form hollowed-out tubes (made of and lined by epithelial cells) and blood cells
PROCESS
● Splanchic mesoderm -> hemangioblast -> blood island
● Inner cells -> HSC -> blood cells
● Outer cells -> angioblasts -> endothelial cells
● Mediated by fgf, vegf, angiopoietins
● IN GENERAL: cords of splanchnic mesodermal cells become aggregated along the future path of a developing vessel
● These cords of cells will form hollowed-out tubes (made of/lined by thin layer of epithelial cells) AND blood cells
● First Phase: Splanchnic mesoderm cells become hemangioblasts and aggregate in blood islands (a). The inner blood island cells become hematopoietic stem cells (c) and generate all blood cell types. Outer cells become angioblasts (b), progenitors to blood vessel cells.
● Second Phase: angioblasts multiply and differentiate into endothelial cells, which line blood vessels.
● Third Phase: Endothelial cells form tubes and connect to form the primary capillary plexus, a network of capillaries.
● Three growth factors involved: basic fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and angiopoietins.

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13
Q
  1. What are the two models for the vascular tube lumen formation? Explain. (you can use diagrams.)
A

Cord hollowing model – membrane of all cells is part of lumen
● Endocytosis creates vacuoles
● Vacuoles merge to become larger
● Larger vacuoles fuse with membrane to form lumen
Cell Hollowing model – each section of lumen is made up of one cell
● Vacuoles form from intracellular lumina of cells
● Individual Lumina fuse at same point in every cell
● Forms a lining that becomes lumen

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14
Q
  1. Which signaling pathway(s) controls angioblast specification?
A
  • Angioblasts are specified: they will form either an artery or a vein
  • Shh from the notochord induces VEGF expression in/from the somites. VEGF acts on neighboring angioblasts to activate Notch signaling pathway; Notch stimulates Gridlock expression, which stimulates ephrin and other arterial markers
  • Arteries form first in response to VEGF; more VEGF more Notch expressed Gridlock expressed ephrin (B2) produced
  • Less Notch  less Gridlock  ephrin receptor (EphB4) is produced  veins
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15
Q
  1. During the formation of the circulatory system, arterial and venous capillaries connect exclusively to each other. How is this accomplished?
A

Interaction between ephrin ligand (ephrin b-2 – artery) and receptor (ephB4 - vein)
● Ensure artery only interact and fuse with veins (and not other arteries)
● In non border areas interaction ensures proper fusing (interaction only in areas where this should occur)
● More than 1 ephrin and ephrin receptor exist because each set has different purpose
○ Ephrinb2 and ephb4 either restrict connection b/w endothelial cells or stimulate formation of new capillary sprouts

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16
Q
  1. Define and briefly explain organ-specific angiogenesis?
A

Schwann cells secrete VEGF that induce endothelial cells to become arteries
a. Arteries induce formation of veins
2. Vascular smooth muscle secrete factor that induce neuron to grow
3. The above occur together and result in nervous system following vascular system
a. Arteries align with peripheral nerves
peripheral neurons and associated Schwann cells secrete VEGF, which induces arteries….

17
Q
  1. Explain briefly the concept of stem cell.
A

● Cell that divides to produce itself and a committed cell
○ Committed cell restricted to certain differentiation fates and can still divide
● The stem cell is unspecialized and can either be pluripotent or totipotent
○ Pluripotent – bone marrow hematopoietic stem cell – give rise to itself and blood cell
○ Totipotent – blastocoel cell – can give rise to all cells and form a zygote on its own (as a result of indeterminate cleavage)
● Progenitor – before migration, multipotent, become precursor during migration
○ Precursor – almost certain fate
● A stem cell is an unspecialized cell that is capable of replicating or self renewing and developing into specialized cells of a variety of cell types. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell. Example of a hematopoietic stem cell producing a second generation stem cell and a neuron.
● A progenitor cell is unspecialized or has partial characteristics of a specialized cell that is capable of undergoing cell division and yielding two specialized cells. Shown here is an example of a myeloid progenitor undergoing cell division to yield two specialized cells (a neutrophil and a red blood cell). A precursor cell is a bit more specialized progenitor cell.

18
Q
  1. What is AGM and what is its role?
A

Aorta-Gonad-Mesonephros (AGM) – visceral lateral plate mesoderm near aorta made from splanchopleure
● Origin of definitive hematopoietic blood stem cells that produce all blood cells except lymphocytes for embryo
● Contribute fetal stem cells to liver that populate bone marrow

19
Q
  1. What are hematopoetic inductive environments and what is their role in the differentiation of HSCs into different lineages?
A

Hematopoietic inductive environment (niches)
● Short range interaction between stromal (mesenchymal) cells and HSC in regions of determination (site of hematopoiesis)
○ Area of extracellular matrix with different Paracrine factors such as cytokines
■ Drive the differentiation of hematopoietic stem cell into pathways
● Role = developmental path is based on HSC encounter with ECM cytokines
○ Affected by chemical, physical, mechnial signals (temperature, ions)

● Different paracrine factors are important in driving the differentiation of HSCs into various pathways.
● Cytokines are involved in blood cell and lymphocyte production.
● They are secreted and concentrated in extracellular matrix of stromal (mesenchymal) cells at the sites of hematopoiesis.
● Developmental path is determined by what cytokines HSCs encounter. Short range interactions between HSC and stromal cells that HSC encounters in regions (niches) of determination is called hematopoietic inductive microenvironments (HIMs).
● ‘Niches’ provide physical support, soluble factors and cell-mediated interactions to maintain and regulate the function of haematopoietic stem cells (HSCs).
● In addition, they can provide physical conditions that are conducive to stem cell renewal and differentiation.
● This schematic represents many of the factors that have been shown recently to be important in the bone marrow haematopoietic niche.
● Cytokines and cell surface adhesion molecules are depicted only generally in this schematic. Instead, this figure emphasizes the many distinct cell populations that contribute to HSC regulation by the niche, and the critical chemical, physical and mechanical signals that can modulate HSC behaviour, including temperature, shear forces, oxygen tension and monoatomic ions, such as Ca2+.
● CAR, CXCL12-abundant reticular; GPCR, G protein-coupled receptor; MPP, multipotent progenitor; MSC, mesenchymal stem cell; RTK, receptor Tyr kinase.

20
Q
  1. What is derived from the endodermal germ layer?
A

● Digestive tube
● Respiratory tube
● Epithelial lining digestive, respiratory

21
Q
  1. Name three organs that develop as outgrowths of the early digestive system and name one function for each of these organs.
A
  1. Name three organs that develop as outgrowths of the early digestive system and name one function for each of these organs.

● Liver – production of bile
● Gall bladder – storage of bile
● Pancreas – production of insulin and glucagon for blood sugar regulation