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1
Q

what arises from the intermediate mesoderm

A

kidneys, gonads, and adrenals

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2
Q

what arises from the lateral plate mesoderm

A

heart, blood vessels, body cavity, and pelvic/limb skeletons

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3
Q

BMP levels of intermediate and LMP (induced)

A

high, further from the neural tube and notochord results in less BMP inhibitors and more BMPs, possibly as a result of differential expression of Fox genes

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4
Q

Pax2

A

specifies intermediate mesoderm

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5
Q

nephron

A

functional unit of the kidney

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6
Q

development of the kidney

A

occurs in 3 stages through reciprocal interactions, only the last stage is the final functional kidney

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7
Q

stages of development of the kidney

A

formation of the pronephros, mesonephros, and then metanephros

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8
Q

formation of the pronephros

A

pronephric duct cells migrate and induce the formation of pronephros, tubules of the initial kidney, which eventually results in the Wolffian duct

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9
Q

formation of mesonephros

A

grow out of the Wolffian duct in the posterior region

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10
Q

formation of metanephros

A

arises from the metanephric mesenchyme at the most posterior region of intermediate mesoderm, which induces branching and the formation of Ureteric buds

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11
Q

what specifies the identity of the kidney?

A

BMP levels and interaction of the paraxial mesoderm, which induces Lim1, Pax2, and Pax8 (which will induce kidneys in other mesoderm cells)

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12
Q

what limits the position of kidney formation?

A

Hox genes, give competence to respond and express Lim1

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13
Q

which interactions result in the final kidney development?

A

reciprocal interactions between the ureteric buds, which become collecting ducts and ureter, and the metanephric mesenchyme, which becomes the nephron. Ureteric bud branches into the metanephric mesenchyme, which then condenses and forms the nephron

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14
Q

how do the different cell populations arise?

A

differences in the time they migrated through the primitive streak

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15
Q

migration that results in Ureteric cells

A

early migration lead to less time exposed to Wnt and more time exposed to posterior FGF9 and RA, so those are high and Wnt is low

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16
Q

migration that results in metanephric mesenchymal cells

A

late migration results in longer exposure to Wnt (higher levels) and lower levels of FGF9/RA, low FGF9 and RA levels make the tissues competent to respond to the signals of the Ureteric bud

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17
Q

mechanisms of the reciprocal induction that forms the kidneys

A
  1. Metanephric mesenchyme signals the ureteric bud to branch off the Wolffian duct through GDFN secretion
  2. Ureteric bud signals the mesenchyme to survive by preventing apoptosis through secretion of Fgf2, Fgf9, and BMP7, results in a population of stem cells
  3. Mesenchyme induces the UB to branch further and further, creating ureteric bud tip cells and mesenchyme cap cells
  4. UB induces the mesenchyme to condense and develop the nephron, bud cells release Wnt signals which triggers MET in condensed cap cells, epithelium undergoes morphogenesis and tubulation to form kidneys
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18
Q

GDNF

A

glial-derived neurotrophic factor (GDNF) that gets secreted from the metanephric mesenchyme and causes outgrowth of the ureteric bud

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19
Q

which signaling factor is necessary for the MET for mesenchyme cells in the kidney

A

Notch (Wnt)

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20
Q

connection of ureter to bladder endoderm

A

to complete the filtration system, the ureter uses Eph-ephrin pathway to find the bladder

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21
Q

location of the LMP

A

furthest from the notochord/NT, lateral to the intermediate mesoderm

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22
Q

layers of the LMP

A

dorsal side is somatic mesoderm, ventral is splanchnic mesoderm, space between them becomes the coelom

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23
Q

development of the circulatory system

A

first functional system to develop in the embryo, arising from the splanchnic (ventral visceral) mesoderm

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24
Q

development of the heart

A

starts in left and right regions which later merge, heart progenitor cells migrate together through the primitive streak and then anteriorly to join the LPM creating the heart fields (cardiogenic mesoderm)

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25
first heart field
forms the scaffold of developing heart as well as the left ventricle, expressing Mesp1 and Nkx2.5
26
second heart field
forms the rest of the heart as well as jaw muscles and lung mesenchyme, expressing Mesp1, Nkx2.5 AND Tbx1
27
contribution of NCCs to heart development
heart forms at the anterior end of the embryo specified by the pharyngeal endoderm and notochord through secretion of BMPs and Fgf8, inhibitors of Wnt and BMPs in the posterior region induce blood formation and prevent posterior heart development
28
migration of cardiac precursor cells
cells migrate posterior along the gut endoderm by following a fibronectin gradient from the gut, each heart field migrates before merging into one, which occurs when the LPM folds to surround the embryo, mutations can prevent fusions, resulting in 2 hearts
29
characteristics of cardiac progenitor cells
express pioneer heart factors Nkx2.5 and Mesp1, derived from earlier mesoderm precursor, and location influences identity, as they have the potential to form hemangioblasts
30
hemangioblats
blood vessels and blood cells
31
cells that arise from cardiac progenitor cells
endocardium, endothelium, smooth muscle, and cardiac muscle
32
formation of blood vessels
2 ways, vasculogenesis and angiogenesis
33
vasculogenesis
begins the job of forming blood vessels from mesoderm hemangioblast cells, requires Fgfs and VEGF-A
34
angiogenesis
finishes the job of vessels by remodeling and branching existing vessels, also requires VEGF-A, which is secreted by developing organs to recruit vessels to form the capillary network
35
endoderm derivatives
GI tract, liver, lining of the organs, and lungs, patterned by overlaying mesoderm
36
major functions of the endoderm
pattern mesodermal tissues, form epithelial layers of digestive and respiratory tubes, and form epithelial layers of certain glands (tonsils, thyroid/parathyroid, and thymus)
37
endoderm structure
initiates as a bulk tube structure stretching from the mouth to the anus that then splits off/ branches into specific structures, touches ectoderm at the mouth and anus only
38
Brachyury/TbxT
mesodermal cells that enter through the primitive streak express these, high BMPs and Fgfs induce TbxT
39
Sox17
endoderm specific, high nodal from the visceral endoderm result in Sox17 as cells leave the primitive streak
40
patterning of endoderm along AP axis
high Wnt, BMPs, and Fgfs in the posterior region due to expression of hox genes, anterior becomes the pharynx, lung, and thyroid, middle becomes the liver and pancreas, and posterior becomes intestine
41
formation of endoderm
begins as a sheet, folding initiates at anterior (anterior intestinal portal AIP) and posterior (caudal intestinal portal CIP) ends and then fuse in the middle, shrinking the yolk sac
42
oral plate
anterior region where endoderm touches ectoderm
43
anorectal junction
posterior region where endoderm touches ectoderm
44
pharynx
digestive tube located anterior to respiratory system, contains pharyngeal arches (meso/ecto) and pharyngeal pouches (endoderm)
45
endoderm pharyngeal pouches give rise to
glands, the tonsils, thyroid/parathyroid, and thymus
46
significance of pharyngeal pouches to NCCs
pharyngeal pouches express Shh which is a survival factor for neural crest cells that migrate through the pouches
47
length of digestive tube
from esophagus to rectum, consists of endoderm (lining of the tube) surrounded by LPM that forms connective tissues and smooth muscles
48
what specifies specifics of endoderm
mesodermal signaling, default state of is stomach like endo, Wnt in the posterior end induces Cdx1 and Cdx2, where high levels specify the large intestine and low levels specify small intestine, Barx1 in the stomach blocks Wnt, so anterior becomes stomach
49
Cdx2 inhibits
stomach, liver, and pancreas
50
stomach txf
Sox2
51
pancreas txf
Pdx1
52
liver txf
Hox
53
small intestine txf
Cdx2
54
large intestine/colon txf
Cdx1
55
what causes differential Hox gene expression along endoderm
endoderm gradient of Shh, AP axis
56
intestinal stem cell
interactions between smooth muscle mesoderm and endoderm keeps stem cells away from villi, stem cells express b-catenin and Sox9, villi only express Sox9
57
relationship between cardiomesoderm and endoderm
reciprocal signaling are critical, endoderm patterns cardiogenic mesoderm and then cardiomesoderm induces liver
58
what directs development of liver and pancreas
endoderm buds interact with mesenchyme, reciprocal signaling, notochord represses liver (high Shh) but allows pancreas to form
59
development of the pancreas
two separate structuress, dorsal and ventral diverticula, that eventually fuse,
60
pancreatic pioneers
Pdx1 and Ptf1a
61
pancreatic cell types
endocrine and exocrine
62
signaling for exocrine
+Notch results in high Ptf1a concentrations, form digestive enzymes
63
signaling for endocrine
-Notch shuts off Ptf1a, activating Ngn3, low Ptf1a, form insulin and glucagon
64
B precursor
cells that will make insulin, patterned further with Pax4
65
a precursor
cells that will make glucagon, patterned further with Arx
66
relationship between Pax4 and Arx
mutually repress each other
67
how could you make b cells using a skin cell in a dish
make it an induced pluripotent stem cell by treating it with Oct4, Nanog, and Sox2, then pattern it as Sox17, Foxa2/HNF1B, Pdx1, low Ptf1a, Pax4

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