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Fall 2022 > Dev Bio Final > Flashcards

Dev Bio Final Flashcards

1
Q

Intermediate mesoderm derivatives?

A

Urogenital system (kidney, gonads)

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2
Q

Lateral Plate Mesoderm derivatives?

A

heart, blood vessels, pelvic and limb skeleton origin of body cavity

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3
Q

Intermediate mesoderm & lateral plate mesoderm are induced by

A

high levels of BMP

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4
Q

High levels of BMP are located

A

further away from Neural Tube

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5
Q

Neural Tube secretes

A

BMP inhibitor

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6
Q

What genes may induce Intermediate & lateral plate mesoderm?

A

Fox genes

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7
Q

Pax2 specifies

A

Intermediate mesoderm

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8
Q

Stage 1 of kidney development

A

Pronephros (tubules of initial kidney)

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9
Q

Pronephros establishes the

A

Wolffian duct

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10
Q

Stage 2 of kidney development

A

Mesonephros

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11
Q

Mesonephros grows out of

A

posterior region of Wolffian duct

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12
Q

Stage 3 of kidney development

A

Metanephros

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13
Q

Metanephros forms from

A

metanephric mesenchyme at the most posterior region of intermediate mesoderm

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14
Q

Metanephros induces

A

ureteric bud & branching

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15
Q

To form kidney, intermediate mesoderm must be in contact with?

A

Paraxial mesoderm

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16
Q

Intermediate mesoderms interaction with paraxial mesoderm induces what?

A

Lim1, Pax2 & Pax8

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17
Q

Lim1, Pax2 & Pax8 are sufficient to induce

A

kidney

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18
Q

What limits the position of kidney formation & gives cells the competency to respond & express Lim1?

A

Hox genes (Hoxb4)

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19
Q

What are the two ‘final’ kidney cell populations?

A

Ureteric bud & Metanephric mesenchyme

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20
Q

Ureteric bud consists of

A

collecting ducts & ureter

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21
Q

Metanephric mesenchyme consists of

A

nephron

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22
Q

Reciprocal induction

A

each induces the other

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23
Q

Ureteric bud branches into the

A

metanephric mesenchyme

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24
Q

How does the Meta mesenchyme responds to the ureteric bud branching?

A

It condenses & forms nephron

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25
Q

What causes the ‘final’ kidney cell populations to differ?

A

the ‘timing’ of the cells migration through the primitive streak

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26
Q

Which cell population of the kidney migrates through the primitive streak early?

A

Ureteric

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27
Q

Which cell population of the kidney migrates through the primitive streak late?

A

Metanephric

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28
Q

Less Wnt + High Fgf/RA induces which kidney cell population?

A

Ureteric

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29
Q

More Wnt + Low Fgf/RA induces which kidney cell population?

A

Metanephric

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30
Q

Low Fgf/RA makes metanephric mesenchyme competent to respond to what?

A

Ureteric bud

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31
Q

Step 1 of kidney development

A

Metanephric mesenchyme signals ureteric bud to branch off Wolffian duct via GDNF secretion (ret receptor)

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32
Q

Step 2 of kidney development

A

Ureteric bud signals (Fgf2, Fgf9, BMP7) mesenchyme to ‘survive’ = stem cell pool

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33
Q

Step 3 of kidney development

A

Mesenchyme induces ureteric bud to branch further, creating the ureteric bud tip cells & mesenchyme cap cells

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34
Q

Step 4 of kidney development

A

ureteric bud induces mesenchyme to condense and develop nephron

Wnt signals from bud cells induce MET in condensed cap cells, which causes the epithelium to undergo morphogenesis & tubulation. Process dependent on Notch expression

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35
Q

Ureter must connect to what to complete the filtration system?

A

bladder

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36
Q

Which pathway does the ureter used to connect to the bladder?

A

Eph-ephrin pathway

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37
Q

What is furthest from the notochord & NT?

A

lateral plate mesoderm

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38
Q

What two layers does the lateral plate mesoderm split into?

A

Somatic mesoderm (dorsal) & Splanchnic mesoderm (ventral)

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39
Q

The space between somatic mesoderm and splanchnic mesoderm is called what?

A

coelom

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40
Q

Dermis & body wall muscles would originate from which layer?

A

the ‘outer’ mesodermal layer

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41
Q

The inner layers of lateral plate mesoderm make up what?

A

organs & surround endoderm (digestive tract)

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42
Q

What is the first functional system to develop in embryo from splanchnic mesoderm?

A

circulatory system

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43
Q

Heart progenitor cells migrate through what?

A

primitive streak

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44
Q

The heart progenitor cells migrating through the primitive streak anteriorly & joining the lateral plate mesoderm creates what?

A

heart fields (cardiogenic mesoderm)

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45
Q

The first heart fields consists of what?

A

scaffold of heart & left ventricle (Mesp1 & Nkx2.5)

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46
Q

The second heart field consists of what?

A

all other parts of heart (not scaffold & left ventricle) & jaw muscles & lung mesenchyme (Mesp1, Nkx2.5, Tbx1)

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47
Q

What contributes to heart development?

A

Neural crest cells

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48
Q

what end of the embryo does the heart form at?

A

anterior end, starting in the ‘neck’ region

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49
Q

What specifies the anterior lateral plate mesoderm?

A

pharyngeal endoderm & notochord; requires BMP & Fgf8

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50
Q

What induces blood formation & prevents heart development in the posterior?

A

Wnt & BMP inhibitors

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51
Q

Developing heart cells migrate posterior along what?

A

gut endoderm

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52
Q

What gradient do heart cells follow along the gut endoderm?

A

fibronectin gradient

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53
Q

When do the heart fields merge together?

A

occurs as Lateral plate mesoderm folds to surround embryo; 7 somite stage

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54
Q

Mutations that prevent heart field fusion result in what?

A

two hearts

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55
Q

What cells can make all the cell types of the heart?

A

Cardiac progenitor cells

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56
Q

What are some of the cell types of the heart?

A

endocardium, endothelium, smooth muscle & cardiac muscle

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57
Q

Cardiac progenitor cells express what pioneer factors?

A

Nkx2.5 & Mesp1

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58
Q

Cardiac progenitor cells are derived from what?

A

earlier mesoderm precursor

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59
Q

hemanigoblasts are

A

blood vessels & blood cells

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60
Q

Vasculogenesis is the

A

creation of vessels from mesoderm (hemangioblast) cells

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61
Q

Vasculogenesis requires what signals?

A

Starts job: Fgfs & VEGF-A

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62
Q

Angiogenesis is when

A

existing vessels are remodeled and branched

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63
Q

Angiogenesis requires what signals?

A

Finishes job: VEGF-A (secreted by developing organs to recruit vessels to form capillary network)

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64
Q

What are the three major functions of endoderm?

A

(1) pattern mesodermal tissues
(2) form epithelial layers of digestive & respiratory tubes
(3) Form epithelial layers of certain glands (tonsils, thymus, thyroid, parathyroid)

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65
Q

Majority of endoderm initiates as what?

A

a bulk structure (tube) that systematically branches out into specific structures; stretches mouth to anus

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66
Q

What must cells express when entering the primitive streak to become endoderm?

A

Sox17

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67
Q

What must cells express when entering the primitive streak to become mesoderm?

A

brachyrury & TbxT

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68
Q

High [Nodal] from visceral endoderm induces the expression of what?

A

Sox17

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69
Q

High [BMP] & [FGF] induces the expression of what?

A

TbxT

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70
Q

Once the endoderm is induced, it is patterned along the A-P axis via what?

A

Wnt/Bmp/fgf (high in posterior) & Hox genes

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71
Q

Anterior region of endoderm gives rise to what?

A

pharynx, lung, thryoid

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72
Q

Middle region of endoderm gives rise to what?

A

liver, pancreas

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73
Q

Posterior region of endoderm gives rise to what?

A

intestine

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74
Q

Endoderm starts as what?

A

a sheet & folds into a tube (like NT)

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75
Q

Folding initiates in two locations (anterior & posterior) then what?

A

It fuses in the middle (like NT closure)

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76
Q

What two sites of the mammalian gut tube migrate toward each other and fuse?

A

Anterior intestinal portal (AIP) & Caudal intestinal portal (CIP)

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77
Q

As the anterior intestinal portal & caudal intestinal portal migrate towards the middle, what slowly shrinks & disappears?

A

the yolk sac

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78
Q

What part of the endoderm is the only region that contacts the ectoderm directly?

A

the ends

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79
Q

What is the anterior region that contacts the ectoderm?

A

oral plate (stomodeum)

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80
Q

What is the posterior region that contacts the ectoderm?

A

anorectal junction

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81
Q

What is the digestive tube anterior to where respiratory starts?

A

pharynx

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82
Q

What are the ectoderm derivatives in the very anterior mouth?

A

teeth, tastebuds

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83
Q

What region of the mouth is endoderm?

A

posterior

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84
Q

The pharynx has what?

A

pharyngeal arches (mesoderm/ectoderm) & pharyngeal pouches (endoderm)

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85
Q

What do the pharyngeal pouches give rise to?

A

specific glands: tonsil, thyroid, parathyroid, thymus

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86
Q

Where does the respiratory system start developing?

A

between the 4th pair of pharyngeal pouches

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87
Q

Shh from endoderm is known as what?

A

survival factor

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88
Q

The digestive tube stretches from where to where?

A

esophagus to rectum

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89
Q

The digestive tube consists of what?

A

endoderm surrounded by lateral plate mesoderm

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90
Q

The endoderm of the digestive tube forms what?

A

lining of tube

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91
Q

The lateral plate mesoderm of the digestive tube forms what?

A

connective tissues and smooth muscles

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92
Q

Patterning of the digestive tube is dependent on what?

A

A-P axis

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93
Q

What is critical for endoderm identity?

A

Sox17

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94
Q

What is the default state of the digestive tube (in terms of differentiation)?

A

anterior/stomach like endoderm

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95
Q

Wnt expression in the posterior of the digestive tube induces what?

A

Cdx1 & Cdx2

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96
Q

High expression of [Cdx1] & [Cdx2] induces what?

A

large intestine

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97
Q

Low expression of [Cdx1] & [Cdx2] induces what?

A

small intestine

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98
Q

Cdx2 inhibits what?

A

stomach, liver, & pancreas

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99
Q

What blocks wnt in the anterior?

A

Barx1

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100
Q

When Wnt is blocked by Barx1 in the anterior, what forms?

A

stomach (mesenchymal signals)

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101
Q

Endoderm secretes what?

A

graded Shh

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102
Q

Graded Shh secretion via the endoderm induces what?

A

differential Hox expression

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103
Q

Once the digestive tube is patterned, what occurs along the A-P axis?

A

synchronized differentiation

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104
Q

What is formed through buckling of tissues via interactions between smooth muscle & endoderm?

A

Villi of intestine

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105
Q

The buckling of tissues positions stem cells away from what?

A

villus tip (facing lumen)

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106
Q

B-catenin & Sox9 expression induce what?

A

intestinal stem cell

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107
Q

The other digestive organs form as what?

A

buds off of endoderm in the posterior region

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108
Q

Buds interact with what to direct development of the liver & pancreas?

A

mesenchyme

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109
Q

Liver bud branches to form what?

A

gallbladder

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110
Q

Early in development endoderm patterns what?

A

cardiogenic mesoderm

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111
Q

Later, cardiac mesoderm induces what?

A

liver and pancreas

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112
Q

Any endoderm near cardiac mesoderm will express what?

A

liver genes (a-fetoprotein & albumin)

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113
Q

What signals are needed to express liver genes?

A

Fgfs (cardiac mesoderm) & BMP (lateral plate mesoderm)

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114
Q

Liver is repressed by what?

A

notochord

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115
Q

Why is liver repressed by the notochord?

A

the notochord inhibits Shh in the area

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116
Q

The endoderm (liver) must be competent for what?

A

to respond to fgf

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117
Q

What factors open chromatin near liver genes?

A

Foxa1 & Foxa2

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118
Q

The liver bud grows into what?

A

mesenchyme & is induced to differentiate into multiple cell types

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119
Q

The pancreas develops from what two separate origins?

A

dorsal & ventral diverticula (outgrowth)

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120
Q

The pancreas is induced by what?

A

notochord

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121
Q

The pancreas is inhibited by what?

A

cardiogenic mesoderm

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122
Q

The notochord secrets what to inhibit Shh in endoderm?

A

Fgf2 & activin

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123
Q

The notochord secretion of fgf2 & activin allows endoderm to respond to what?

A

blood vessels

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124
Q

What is induced at the foreguts 3 contact points with the endothelium of vessel?

A

Pdx1 & ptf1a

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125
Q

No vessels =

A

no pancreas

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126
Q

extra vessels =

A

large pancreatic tissue

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127
Q

What sets up the pathway to insulin-secreting cells?

A

Pdx1

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128
Q

Pancreatic stem cells are regulated by what levels?

A

Ptf1a

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129
Q

high [Ptf1a] induces what?

A

exocrine (digestive enzymes)

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130
Q

low [Ptf1a] induces what?

A

endocrine (insulin, glucagon)

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131
Q

Notch signaling plays a role in what?

A

determining cell types of the foregut

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132
Q

+ Notch induces what?

A

exocrine (keeps Ptf1a on)

133
Q

(-) Notch induces what?

A

endocrine (shuts off Ptf1a, activates Ngn3)

134
Q

What foregut cell type has another choice after Notch specification?

A

endocrine cells

135
Q

The respiratory tube forms from what?

A

a separation off of the foregut endoderm; i.e. lungs are derived from the digestive system

136
Q

At the level of 4th pharyngeal pouch, what begins to extend ventrally?

A

laryngotracheal groove or respiratory diverticulum

137
Q

The foregut tube becomes what in the digestive system?

A

esophagus

138
Q

The laryngotracheal tube becomes what in the respiratory system?

A

trachea

139
Q

Separation of the foregut tube and laryngotracheal tube requires what?

A

interactions with surrounding mesenchyme

140
Q

Wnt from the ventral mesenchyme induces what?

A

increased B-catenin in endoderm

141
Q

Increased B-catenin in endoderm instructs what in the respiratory system?

A

lung/trachea

142
Q

If B-catenin is expressed in gut tube then what happens?

A

ectopic lungs

143
Q

Dorsal mesenchyme expresses what?

A

Barx1

144
Q

Barx1 induces cells to what?

A

secrete wnt inhibitors

145
Q

Cells secreting wnt inhibitors induces what?

A

esophageal development

146
Q

When the trachea hits the thorax what occurs?

A

instructed to branch

147
Q

What induces further branching of the trachea after the thorax is reached?

A

mesenchyme in the region

148
Q

lung mesoderm =

A

branches (right)

149
Q

If lung mesoderm is replaced by tracheal mesoderm what occurs?

A

less branching (left)

150
Q

What are the three steps of bronchial branching?

A

(1) Domain branching
(2) Planar bifurcation
(3) orthogonal bifurcation

151
Q

Domain branching

A

proximal-distal outgrows in dorsal, ventral, medial, & lateral positions (spiraling comb)

152
Q

Planar bifurcation

A

tip of each new branch split at midline along A-P axis

153
Q

Orthogonal bifurcation

A

tip of branch splits at 90 rotation

154
Q

Each alveolus can be traced back to what?

A

original bronchus

155
Q

Branching can be caused

A

externally or internally

156
Q

External (mammalian lungs)

A

smooth muscle develops in surrounding mesoderm & compresses the bud into two forks (bifurcation)

157
Q

Internal (avian lungs)

A

branch bud induced by localized apical constriction along parental branch (domain branching)

158
Q

In both cases (internal & external) branching is induced by what?

A

Fgf signaling from mesenchyme

159
Q

Alveolar cells secrete what?

A

surfactant

160
Q

surfactant

A

keeps alveolar cells from sticking together

161
Q

Surfactant triggers what?

A

mothers immune system

162
Q

Macrophages migration from fetus to uterine lining triggers what?

A

a cascade of IL1B to prostaglandins, which induces contraction

163
Q

Limbs forms at predefined along

A

A-P axis

164
Q

Limb Bud

A

forms and grows outwards

165
Q

Thumb =

A

anterior

166
Q

Pinkie =

A

posterior

167
Q

Proximal-Distal axis of limbs

A

Shoulder to fingers or hip to toes

168
Q

Stylopod

A

most proximal (connected to girdle)

169
Q

Zeugopod

A

middle

170
Q

Autopod

A

most distal

171
Q

Each segment is regulated genetically by

A

Hox genes

172
Q

First identifiable sign of limb development

A

limb bud

173
Q

limb bud arises from what?

A

limb field

174
Q

All cells are capable of making a limb where?

A

in limb field

175
Q

Limb bud is derived from what?

A
  • LPM (skeletal)
  • Somites (muscle)
  • Overlying ectoderm (epidermis)
176
Q

Limb bud grows what?

A

proximal-distal (limited in A-P & D-V growth)

177
Q

Limb bud is organized into three domains. What are these domains?

A

1) Progress Zone (PZ)
2) Zone of polarizing activity (ZPA)
3) Apical Ectodermal Ridge (AER)

178
Q

Progress Zone (PZ)

A

high proliferation; making cells that will contribute to the limb

179
Q

Zone of polarizing activity (ZPA)

A

posterior region; patterns the A-P axis

180
Q

Apical ectodermal ridge (AER)

A

thickening of ectoderm; critical signaling center (all axes of the limb)

181
Q

What patterns the mesoderm to initiate a specific pathway?

A

Hox genes

182
Q

What is later used for the P-D identity within the limb?

A

Hox genes

183
Q

Hox expression follows what?

A

3’ to 5’ expression

184
Q

3’ hox genes =

A

more proximal

185
Q

Hox9/10

A

stylopod

186
Q

5’ hox genes =

A

more distal

187
Q

Hox12/13

A

autopod

188
Q

What happens if Hox10 is knocked down in a mouse?

A

Hox9 in the forelimb would be enough to give some stylopod in the forelimb but no hindlimb would form due to lack of Hox9 expression

189
Q

Hox gene expression along the P-D axis contributed to the evolution of what?

A

tetrapod limb development

190
Q

Tiktaalik =

A

’ fish with fingers’
- first tetrapod-like fossil; had joints that allowed flexion

191
Q

Regional specification of mesoderm for forelimb?

A

Hoxc6 near the cervical- thoracic transition

192
Q

Regional specification of mesoderm for hindlimb?

A

Hoxd9 near the lumbar-sacral transition

193
Q

Expanding the Hox6 region (forelimb) mesoderm leads to what?

A

expanded limb bud

194
Q

Decreasing Hoxc6 region (forelimb) mesoderm leads to what?

A

reduced limb bud

195
Q

What allows an entire limb to be developed experimentally or “naturally”?

A

potency

196
Q

RA represses what?

A

fgf8

197
Q

RA represses fgf8 in specific regions leads to what?

A

forelimb positioning

198
Q

RA expression in what?

A

trunk mesoderm

199
Q

Fgf8 expression in what?

A

anterior & posterior

200
Q

Loss of RA leads to what?

A

expanded fgf8; leads to loss of Tbx5; leads to hindlimb

201
Q

RA is not necessary for what?

A

hindlimb development

202
Q

Limb types are specific to what?

A

Tbx expression

203
Q

If an ectopic limb is induced what is key?

A

position

204
Q

Tbx5 =

A

forelimb

205
Q

Loss of Tbx5 =

A

no forelimb

206
Q

Pitx1, Tbx4, Islet1 =

A

hindlimb

207
Q

Loss of Tbx4 =

A

outcome is species dependent
- chick = no hindlimb
- mouse = initial growth; premature arrest

208
Q

If an fgf10 bead is placed between the forelimb & hindlimb what happens?

A

bud will express both Tbx5 & Tbx4; leads to chimera limb; ectopic limb will have both identities

209
Q

Loss of Islet1 leads to what?

A

no hindlimb (formation of limb bud)

210
Q

Loss of Pitx1 leads to what?

A

abnormal patterning

211
Q

Islet1

A

hindlimb initiation

212
Q

Pitx1

A

hindlimb patterning

213
Q

Tbx4

A

hindlimb outgrowth

214
Q

Islet1, Pitx1, & Tbx4 converge on what?

A

fgf10 (induces proliferation of limb)

215
Q

What happens once the limb field is induced? what is it induced by?

A

lateral plate mesoderm undergoes EMT
- Tbx5

216
Q

specified fields set up two gradients. What induces these gradients?

A

Wnt signaling
- fields maintain each others expression via 2 positive feedback loops
- keeps proliferation high so the limb bud will grow

217
Q

Fgf10 in messenchyme induces what?

A

ectoderm to express fgf8

218
Q

Apical ectodermal ridge (AER) induces what?

A

Fgf8 expression

219
Q

Apical ectodermal ridge (AER) does what?

A
  • patterns all axes of the developing limb
  • Proliferation in underlying mesenchyme (progress zone - PR)
  • maintains gene expression for the A-P axis
  • directs differentiation across axes
220
Q

Extra AER =

A

extra/duplicate limb

221
Q

No AER =

A

no limb

222
Q

AER over the wrong mesenchyme =

A

fate of mesenchyme takes priority

223
Q

AER replaced with fgf8 bead =

A

same as having AER (normal)

224
Q

AER directs mesenchyme to grow BUT what?

A

the mesenchyme retains its patterned identity

225
Q

Mesenchyme what as it grows proximal to distal?

A

ages

226
Q

Early mesenchyme is not as what as late mesenchyme?

A

differentiated

227
Q

What is critical for proper bone development?

A

balance between opposing P-D gradients

228
Q

What signals come from distal?

A

Fgf/Wnt

229
Q

More fgf/wnt exposure

A

more autopod/distal phenotype

230
Q

What signals come from proximal?

A

RA

231
Q

More RA exposure

A

more stylopod/proximal phenotype

232
Q

Graft limb: If left untreated

A

bones will develop as the age of the mesenchyme indicates

233
Q

Graft limb: If RA is added

A

bones become more proximal because proximal genes are induced

234
Q

Graft limb: If fgf/wnt is added

A

bones become more distal because distal genes are induced

235
Q

RA and fgf are what?

A

mutually antagonistic

236
Q

As AER moves distal, more what can be expressed?

A

fgf8

237
Q

Fgf8 upregulates what?

A

Cyp26

238
Q

Cyp26

A

degrades RA

239
Q

RA and fgf8 differentially regulate what?

A

P-D axis

240
Q

Limb fields are what?

A

pre-set

241
Q

RA from trunk mesoderm induces what?

A

Meis1/2 expression; stylopod

242
Q

As AER moves distal what is activated?

A

Hox11 with the RA-fgf8 threshold

243
Q

At the most distal area what is open & expressed?

A

Hox13

244
Q

How do the cells know what type of bone to make?

A

the cell types are the same, but spatially different

245
Q

Alan turing

A

mathematical model of self-organizinng pattterns

246
Q

Activators (A) and Inhibitors (I) are initially what?

A

uniform will eventually create a pattern

247
Q

If A induces A and I then what?

A

I will turn and inhibit A

248
Q

Local diffusion rates will establish what?

A

specific gradients & patterns

249
Q

AER divides the limb into what?

A

2 active domains & 1 inhibitory zone

250
Q

Inhibitory zone (apical zone/ most distal mesenchyme)

A

chondrogenesis is repressed here

251
Q

Active zone (most proximal to inhibitory zone)

A

chondrogenesis occurs

252
Q

Active zone has what?

A

activators and inhibitors of cartilage formation

253
Q

Active zone formed aggregates makes what?

A

cartilage & repress other cells from making it

254
Q

Frozen zone (further from the inhibitory zone)?

A

cartilage is already formed here

255
Q

In the early bud

A

only room from one condnensate

256
Q

In later bud

A

room for 2 (radius & ulna)

257
Q

In latest bud

A

room for many (wrist & digits)

258
Q

Zone of polarizing activity (ZPA)

A

posterior region of the limb bud

259
Q

ZPA is potent enough to produce what when transplanted to the anterior limb bud?

A

new A-P axis

260
Q

ZPA secretes what from posterior to anterior?

A

Shh gradient

261
Q

Expressing Shh in the anterior has the same effect as what?

A

transplanting the entire ZPA

262
Q

What is Shh doing?

A

Shh-expressing cells do not undergo apoptosis & contribute to bone and cartilage of the posterior limb
- Digits 4 & 5 (ring finger + thumb)

263
Q

Digit identity (4 or 5) dependent on what?

A

time of Shh expression, not amount

264
Q

what is independent of Shh?

A

thumb

265
Q

What is the default digit in the absence of Shh?

A

thumb

266
Q

Shh has 2 functions

A

1) pattern digits as a morphogen
2) promote proliferation as a mitogen

267
Q

Shh TxF induces what?

A

Gli1

268
Q

How does Shh pattern digit identity?

A

Cell cycle control & BMP pathway

269
Q

Gli1 regulates what? promotes what?

A
  • regulates cell proliferation of cartilage precursor
  • promotes cartilage formation
270
Q

Division slows through what?

A

decreased Cdk6

271
Q

Gli1 inhibits what?

A

Gremlin (BMP antagonists); thus, active BMP

272
Q

Graded BMP expression across the limb bud leads to what?

A

digit identity (which is then further specified by the webbing between digits)

273
Q

Web mesoderm patterns the digits what to it?

A

anterior
- default is to become 1

274
Q

Gradients are set up through interaction between the what?

A

AER & ZPA

275
Q

What forms a feedback loop from AER?

A

Fgf10 & fgf8

276
Q

BMPs inhibits what?

A

fgfs

277
Q

In the ZPA what induces Gremlin (BMP inhibitor) , which blocks BMPs in limb mesoderm ?

A

Shh

278
Q

Gremlin helps to maintain what?

A

Fgf expression
- fgf inhibits Shh repressors (Etv4/5)

279
Q

Interactions between AER and ZPA creates what?

A

Shh-Fgf feedback loop

280
Q

In anterior what blocks Shh?

A

fgf

281
Q

Eventually, what levels will get really high, inhibiting gremlin, leading to BMP activity increase & fgf ultimate shut down?

A

fgf

282
Q

AER continues to grows what? so what becomes spatially distanced?

A

distally; signaling centers

283
Q

Mutual activation (and repression) stops

A

AER & ZPA disappears

284
Q

Phased Hox expression for limbs; first phase:

A

P-D axis for stylopod and zeugopod

285
Q

Phased Hox expression for limbs; second phase

A

A-P axis for autopod

286
Q

Hox activated by what?

A

‘phased’ enhancers

287
Q

What sets up the 3’ to 5’ hox expression

A

early limb control regulatory (ECLR)

288
Q

ECLR is activated by what?

A

ZRS (ZPA regulatory sequence)

289
Q

Shh flips the script for what?

A

phase 2

290
Q

What Hox is expressed first?

A

5’ hox (Hox13 is most anterior = thumb)

291
Q

Hoxd13

A

most highly expressed

292
Q

D-V axis is determied by what?

A

overlaying ectoderm

293
Q

Swapping the ectoderm in the limb bud does what?

A

reversed D-V axis

294
Q

Wnt7a

A

dorsal ectoderm expression
- first known D-V gene in the limb bud

295
Q

Loss of Wnt7a

A

ventral identity in dorsal (foot pads on top of the foot)

296
Q

Wnt7a induces what?

A

Lmx1b in mesenchyme

297
Q

Lmx1b in mesenchyme specifies what?

A

dorsal expression of Lmx1b in ventral, converts to dorsal (including the underlying tissues (i.e. tendons))

298
Q

Loss of Lmx1b

A

ventralizes the limb

299
Q

human Lmx1b mutations

A

nail-patella syndrome

300
Q

D-V identity is critical for what?

A

the innervation of the tissue

301
Q

Axon pathfinding requires what?

A

D-V cues

302
Q

Ventral ectoderm expresses what?

A

engrailed-1 (En1)

303
Q

Engrailed-1 (En1) represses what? Induces what?

A
  • Represses Wnt in the ectoderm
  • Induced by BMP in ventral mesenchyme
304
Q

What phenotype would you expect in a BMP null mutant here?

A

nail all around

305
Q

D-V axis is coordinated with what?

A

A-P & P-D axis

306
Q

Wnt7a mutants lose what?

A

posterior digits due to reduced Shh expression

307
Q

Wnt7a + Fgf4 induces what?

A

Shh

308
Q

BMPs

A

stops growth and patterning in all 3 axis
- shut down AER as the limb extends
- Shut down ZPA indirectly
- block wnt in the D-V axis

309
Q

Exogenous BMP in AER induces what?

A

epithelialization of tissue

310
Q

Loss of BMPs in AER

A

limb will continue to grow beyond normal

311
Q

All forming digits have what?

A

tissue between them

312
Q

Other organisms lose the tissue between the digits through apoptosis

A

interdigital necrotic zone

313
Q

Apoptosis is required for what?

A

the separation of zeugopod bones & other shaping of the limbs

314
Q

Separation of digits is signaled by what?

A

BMP (induced by RA expression in these tissue)

315
Q

BMPs are inhibited in what?

A

‘non-apoptotic regions’

316
Q

Cartilage-producing cells express what?

A

Noggin (BMP inhibitor)

317
Q

What happens if Noggin is expressed throughout the limb bud?

A

keep the webbing between digits

318
Q

BMP means?

A

bone morphogenetic protein (first decribed as inducers of bone development)

319
Q

Apoptosis vs bone is based on what?

A

context dependency

320
Q

before cartilage condensation

A

BMPs induce apoptosis

321
Q

After cartilage condensation

A

surrounding cells express BMP & induce more cartilage formations

322
Q

Noggin limits what?

A

amount of cartilage induced

323
Q

What is expressed between bones and is required for instruction of joint tissue?

A

GDF5 (BMP)

324
Q

Limb structure/differences are shaped through what?

A

differential regulation of same genes (BMPs, fgfs, Shh)

325
Q

Ducks express what between digits, inhibiting apoptosis?

A

Gremlin (gives them webbed feet)

326
Q

Cetaceans reduce what in hindlimbs?

A

Shh (reduces limb)

327
Q

Snakes lost what?

A

ZRA = no ZPA = no Shh = no limbs

328
Q

Cetaceans increased what in AER leads to longer digits?

A

fgf

Fall 2022 (4 decks)

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