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Embryology > Cell Basis Of Embryo > Flashcards

Cell Basis Of Embryo Flashcards

1
Q

Stem cells have the property of __-__ through symmetric or asymmetric cell divisions

A

Self renewal

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2
Q

What can stem cells give rise to

A

All differentiated cell types in the body (totipotent or pluripotent)

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3
Q

Embryonic stem cells(ESC) what are they derived from

A

Inner cell mass of the blastula

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4
Q

What are ESC and what can they give rise to

A

Pluripotent and give rise to all differentiated cell types from the ectoderm, endoderm, and mesoderm, the primary germ layers, but do not contribute to extraembryonic tissues

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5
Q

What do ESC express

A

Transcription factors
SOX2 and OCT4, Nanog, FoxD3they repress differentiation

-GCNF is required for early stages of pluripotent cell differentiation
Crypto and GDF3 are growth factors found in pluripotent cells

Regulated by oct3/4 sox2, myc and klf4

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6
Q

Adult stem cells: where are they found

A

In differentiated tissues and organs thatundergo rapid regeneration, such. As bone marrow, hair follicles, and intestinal mucosal epithelium

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7
Q

However, there are nests of adult stem cells in may other tissues, including those that have been previously considered nonregnerative, such as the central nervous system and retina

A

These stem cell populations are small and located in the subventricular zone and ciliary margins, respectively

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8
Q

Where are hematopoietic stem cells

A

Derived from bone marrow, peripheral blood, and umbilical cords

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9
Q

What are hematopoietic stem cells used for

A

Treat primary immunodeficiency and various inherited metabolic disorders and as a rescue strategy following marrow destroying cancer treatments

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10
Q

Cancer stem cells

A

Have becomes evident through study of leukemia’s and solid tumors. They are resistant to cancer treatments such as radiation or chemotherapy

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11
Q

What cell surface markers do CSC have

A

CD133 in solid tumors

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12
Q

What is the focus on CSC research

A

Eradicating them, in addition to standard therapies in order to increase cure rates

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13
Q

It is possible to harness the power of stem cells to repair degenerative disorders like Parkinson and ischemia, but why is it limited

A

Sources of stem cells

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14
Q

Induced pluripotent stem cells (iPS)

A

De differentiating somatic cells such as epithelial cells and fibroblasts from adults

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15
Q

What transcription factors can reprogram differentiated cells into pluripotent cells

A

OCT3/4, SOX2, KLF4, Nanog

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16
Q

IPS stem cells have the capacity for self renewal, cell death, or to become progenitors. What can progenitors do

A

Limited capacity for self renewal, but also can differentiate into various cell types or undergo cell death

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17
Q

Histone methylation is done by __ __

A

Histone methyltransferases (writers)

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18
Q

What is methylated

A

Histone Lysine arginine

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19
Q

Is methylation activating or repressing

A

Can be both

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20
Q

Example of Histone activation

A

Trimethylation of lysine 4 on Histone 3 (H3K4me3)

Active promoters

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21
Q

Example of methylation repressing

A

Trimethylation of lysine 9 on Histone 3 (H#K9me3) repressed promoters

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22
Q

Acetylation of Histone

A

DNA is less tightly bound to acetylated histones, thus allowing more open access of transcription factors and other proteins to the promoters of their targets
Activation of gene transcription

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23
Q

Phosphorylation of histones

A

Also leads to an opening of the chromatin structure and activation of gene transcription

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24
Q

Acetylation and phosphorylation are both read by ___ proteins and ___ ___ __ proteins

A

Bromodomain

Pleckstrin homology

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25
Q

Where is DNA methylated

A

CpG islands where cytosine and guanine are directly paired

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26
Q

Where are CpG islands usually located

A

Proximal promoter regions of genes

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27
Q

DNA methylation at CpG islands leads to what

A

Reduced gene expression

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28
Q

DNA hypomethylation at CpG islands

A

Gene overexpresion

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29
Q

Methyl-CpG-binding protein 2(MECP2)

A

Mutated in the neurodevelopmental disorder Rett syndrome, function as readers by binding to methylated DNA and subsequently assembling protein complexes that repress gene expression

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30
Q

What are some disorders of chromatin remodeling

A

Rett, Rubinstein-Taybi, alpha-thalassemia/X linked mental retardation syndromes

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31
Q

What are basic helix-loop-helix transcription factors

A

BHLH genes are a classs of transcription factors that regulate cells ate determination and differentiation in many different tissue during development

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32
Q

BHLH proteins contain a __(_charged) DNA binding region that is followed by two a helices that are separated by a loop

A

Basic +

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33
Q

In BHLH the a helices have. ___ and a __ side (amphipathic)

A

Hydrophilic and hydrophobic

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34
Q

The hydrophobic side of the a helix

A

Motif for protein-protein interactions between different members of the BHLH family
MOST CONSERVED

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35
Q

BHLH proteins often bind to other BHLH proteins (__) to regulat transcription

A

Heterodimer I’ve

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36
Q

BHLH heterodimers are composed of tissue specific BHLH proteins bound to ubiquitously expressed BHLH proteins

A

Ok

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37
Q

How can the prodifferentiation effects of BHLH genes be repressed

A

Inhibitor of differentiation proteins (Id) proteins are HLH proteins that lack the basic DNA binding motif. When Id proteins heterodimerize with specific BHLH proteins, they prevent binding of these BHLH proteins to their target gene promoter sequences (called E boxes)

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38
Q

Growth factors which tend to inhibit differentiation, ___ the level of Id proteins that sequester bHLH proteins which inhibits their ability to bind DNA

A

Increase

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39
Q

In addition , growth factors can stimulate the phosphorylation of DNA binding domain of bHLH proteins which does what

A

Inhibits their ability to bind DNA

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40
Q

BHLH genes are crucial for development of tissues such as muscle(__/__) and neurons (__/__) in humans

A

MyoD/Myogenin

NeuroD/Neurogenin

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41
Q

MyoD

A

Can transdifferentiate several different cell lines into muscle cells
MASTER REGULATOR of muscle differentiation

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42
Q

Knockout MyoD and other bHLH, Myf5

A

Crucial for the differentiation of precursor cells into primitive muscle cells (myoblasts)

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43
Q

Mash1/Ascl1 and Neurogenin1

A

Proneural genes that regulate the formation of neuroblastoma from the neuroepithelium

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44
Q

Mash1/Ascl1 knockout

A

Defects in forebrain development

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45
Q

Neurogenin1 knock out

A

Defects in cranial sensory ganglia and ventral spinal cord neurons

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46
Q

Muscle and neuronal differentiation are controlled by a cascade of ___ genes that function at early and at late stages of cellular diferentiation

A

BHLH

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47
Q

The differentiation of muscle and neuronal cells are inhibited by what pathway

A

Notch

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48
Q

Pax genes all contain conserved ___ DNA binding motifs called the Pax domain, and most Pax family members also contain a ___

A

Bipartite

Homeodomain

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49
Q

PAX proteins do what

A

Repress or activate transcription of target genes

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50
Q

Pax6

A

Eye development drosophila

Aniridia and Peters anomaly in humans

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51
Q

In human eye diseases, the level of PAX6 expression seems to be crucial because why

A

Patients with only one functional copy(haploinsuffiency) have ocular defects and patients without PAX6 function are anophthalmic

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52
Q

PAX3 and PAX7encode both what

A

Homeodomain and PAX DNA binding domains

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53
Q

Rhabdomyosarcoma

A

Results from translocation that results in the formation of a chimeric protein wherein PAX3 and PAX7 is fused to the strong activating domains of the Forkhead family transcription factor FOXO1

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54
Q

Waardenburg syndrome type 1 (AD)

A

Mutation in PAX3 gene

Hearing deficits, ocular defects, and pigmentation abnormalities best typified by. A white forelock

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55
Q

HOX/Homeobox proteins

A

Mutations -dramatic phenotypes such as antennapedia gene, in which legs instead of antennas sprout

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56
Q

In humans and drosophila, the order of HOX genes along the chromosome is

A

Conserved

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57
Q

Defect in HOXA1

A

Impair human neural development

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58
Q

HOXA13 and HOXD13 mutations

A

Limb malformations

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59
Q

All HOX genes contain a __ base pair sequence, the homeobox which encodes what

A

180

A 60 aa homeodomain composed of 3 a helices

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60
Q

The third a helix of the homeodomain does what

A

Binds to DNA sites that contain one or more binding motifs int he promoters of their target genes

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61
Q

Mutations in DNA binding region of homeobox gene NKX2.5

A

Cardiac atrial septal defects

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62
Q

Mutations in ARX

A

Central nervous system malformation syndrome known as lisencephaly

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63
Q

Notch signalling pathway

A

Integral for cell fate determination, including maintenance of stem cell niches, proliferation, apoptosis, and differentiation
Essential for all aspects of organ development through regulation o lateral and inductive cell cell signaling

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64
Q

What are notch proteins

A

Single transmembrane receptors that interact with membrane bound notch ligands (delta like ligands and serrate like ligands) on adjacent cells

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65
Q

In notch, ligand receptor binding triggers proteolytic events leading to the release of the notch intracellular domain (NICD). What happens when NICD translocates to the nucleus

A

Series of intranuclear events culminates in raw induction of expression of a transcription factor that maintains the progenitor state of the cell

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66
Q

In notch, lateral inhibition ensures the correct number of two distinct cell types from a population of cells with equivalent developmental potential

A

Ok

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67
Q

Notch: in the initial cell cell interaction, notch receptor signaling maintains one cell as an uncommitted progenitor

A

Ok

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68
Q

The adjacent cell maintains reduced notch signaling and undergoes differentiation

A

Inductive signaling with other surrounding cells expressing morphogens may overcome a cells commitment to a default fate and lead to an alternative cell fate

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69
Q

Mutations in Jagged1 (notch)

A

Alagille syndrome (arteriohepatic sysplasia) withe liver, kidney, and that notch3 gene mutations are found in CADSIL, an adult vascular degenerative disease with a tendency to early age onset of stroke like events,

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70
Q

During embryogenesis, signalling through )) is crucial for normal development and affects many different processes such as what

A

Growth of new blood vessels, cellular migration , And neuronal atonal guidance

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71
Q

Growth factors generally promote cellular proliferation, migration and survival

A

During embryogenesis, signaling through FTKs is crucial for normal development and affects many different processes such as the growth of new blood vessels, cellular migration, and neuronal atonal guidance

72
Q

What binds to RTK

A

Insulin, epidermal growth factor, nerve growth factor, neurotrophins, platelet derived growth factor

73
Q

What are the 3 domains of RTK

A

Extracellular ligand binding domain

Intracellular kinase domaintransmembrane domain

74
Q

RTK are _ in the unbound state and __ whene bound to ligand

A

Monomer

Domers

75
Q

What does dimerization upon binding to a ligand do for RTK

A

Brings two intracellular kinase domains in close proximity such that one kinase domain can phosphorylation and activate the other (transphosphorylation) which is required to activate the receptor..

76
Q

What happens after RTK transphosphorylation

A

Series of intracellular signaling cascades.

77
Q

What happens if there is an inactivating mutation of one resceptor subunit kinase domain of RTK

A

Abolishment of signaling

78
Q

Mutation in the kinase domain of VEGF receptor 3 (VEGFR3)

A

AD

Inherited lymphatic disorder called Milroy disease

79
Q

What do growth factors do

A

Promoter cellular proliferation, migration and survival

80
Q

During development, RTK is crucial for normal development. What does it effect

A

Different processes, such as growth of new blood vessels, cellular migration and neuronal atonal guidance

81
Q

What do hemangioblasts give rise to

A

Hematopoietic cell and endothelial cell

82
Q

The early endothelial cells proliferate and eventually coalesce to form the first primitive __ ___. What is this called

A

Blood vessels

Vasculogenesis

83
Q

What happens after the first blood vessels are formed

A

Intensive remodeling and maturation into the mature blood vessels in a process called angiogenesis

84
Q

Vasculogenesis

A

Formation of vessels

85
Q

Angiogenesis

A

Maturationa nd remodeling of blood vessels

86
Q

Angiogenesis involves the recruitment of vascular __ __ cells to the vessels to stabilize them

A

Smooth muscle

87
Q

Vasculogenesis and angiogenesis are both dependent on the function of two distinct __ classes, members of the ___ and ___ receptor families

A

RTK
VEGF
Tie

88
Q

__ is essential for endothelial and blood cell development

89
Q

VEGFA knock out

A

Fail to develop blood or endothelial cells and die at an early embryonic stage

90
Q

___ is crucial for development of lymphatic endothelial cells

91
Q

VEDGA signals through three receptors, where are they and what are they’re

A

VEGFR-1, 2 and 3

On endothelial cells

92
Q

The process of angiogenesis refinement depends not he function of angiopoitein/tie2 signaling pathway

A

Tie2 is a RTK that is specifically expressed by endothelial cells and angiopoietin 1 and angiopoietin 2 are its ligands that are expressed by surrounding vascular smooth muscle cells

93
Q

What kind of signaling it angiopoietin/tie2

94
Q

Both VEGF/VEGFR3 and angiopoietin/tie2 are co-opted by __ to stimulate growth of new blood vessels

A

Tumors , which in turn stimulate their growth and metastisis

95
Q

Wnt

A

Morphogen, 19 wnt family members control several processes during development
Establish cell polarity, proliferation, apoptosis, cell fate specification, and migration

96
Q

B-catenin wnt pathway

A

Wnt binds to 1 of 10 frizzled seven transmembrane domain cell surface receptors, and with low density, lipoprotein receptor-related proteins 5 and 6 (LRP5/LRP6) coreceptors,t thereby activating downstream intracellular signaling events

97
Q

Absence of Wnt binding

A

Cytoplasmic B catenin is phosphorylation by glycogen synthase kinase 3 (GSK-3) and targeted for degradation

98
Q

In the presence of wnts , GSK3 is inactivated and B catenin is not phorphorylated . What happen

A

B catenin accumulated in the cytoplasm and translocated to the nucleus where it activates target gene transcription in a complex with T cell factor transcription in a complex with T cell factor transcription factors
(TCF)

99
Q

Bcatenin/TCF target genes

A

VEGF and matrix metalloprotease

100
Q

Dysregulated Wnt

A

Developmental disorders
William-beuren syndrome (heart, neurodevelopmental, and facial defects)
Cancer

101
Q

LRP5 mutations

A

In osteoporosis -pseudoglioma syndrome -congenital blindness and juvenile osteoporosis

102
Q

Shh and Wnt mutations

A

Medulloblastoma , a common malignant brain tumor

103
Q

Sonic hedge hog shh

A

Secreted morphogens critical for early patterning, cell migration and differentiation of many cell types and organ systems

104
Q

Receptor for shh

A

Pathed (PTCH), a transmembrane domain protein

105
Q

Absence of shh

A

Patched inhibits transmembrane domain, G protein linked protein(smoothened smo)

106
Q

Inhibition of smo

A

Inhibits downstream signaling to the nucleus by shh

107
Q

Presence of shh

A

Ptc inhibition is blocked and downstream events follow, including transcriptional activation of target genes such as ptc1, engrailed and others

108
Q

Post translational modification of shh affects what

A

It’s association with the cell membrane, formation of shh multi era, and movement of shh which alters its distribution and concentration gradients

109
Q

Shh is secreted in high levels in the ___

110
Q

The concentration of shh is highest where and lowest where

A

In the floor plate of the neural tube and loft plate

111
Q

What is high in the roof plate

A

Where members of tgfb

112
Q

The cell fates of the ventral interneuron classes and odor neurons are determined by the relative shh concentrations in the tissue and other factors

113
Q

Mutations of shh and ptch

A

Holoprosencephlay -fusion of the two cerebral hemispheres, dorsalization of forebrain structures and anopthalmia or cyclopia

114
Q

___ sidrupts shh signaling

A

Cycloplamine

115
Q

Gorlin syndrome

A

Germline mutation in ptch

Constellation of congenital malformations mostly affecting epidermis, craniofacial structures and nervous system

116
Q

Mutations in GLI3, encoding a zinc finger that mediates shh signaling

A

AD polydactylyl syndromes

117
Q

What happens when GLI translocated to nucleus

A

Activate target gene with CBP

118
Q

What us sufu

A

Suppressor of fused

119
Q

Tgfb superfamily includes what

A

Tgfb, bmp, and activin

120
Q

What do tgfb superfamily do

A

Establish dorsoventral patterning, cell fate decisions, and formation of specific organs and systems, including kidneys , nervous system, skeleton, and blood

121
Q

In humans what are the three forms of TGFB

A

TGFB1, 2, 3

122
Q

What happens when tgfb superfamily bind to ligands to transmembrane kinase receptors

A

Phosphorylation of intracellular receptor associated Smad proteins (R-Smads)

123
Q

Smad proteins

A

Large family of intercellular proteins that are divided into the press classes

124
Q

What are the three classes of Smad

A 
Receptor activated (R-Smads)
Common partner(Co-Smads)
Inhibitory (I-smads)
125
Q

R-Smad/Smad4

A

Regulate target gene transcription by interacting with other proteins or as transcription factors by direct binding to dna

126
Q

What is the bioactive form of vitamin a

A

Retinoids acid

127
Q

How it retinoids acid formed from vitamin a

A

Enzymatic oxidation by retinol aldehyde dehydrogenase and subsequently retinal aldehyde dehydrogenase

128
Q

Free levels of retinoids acid can be modulated by cellular retinoids acid binding proteins which ___ it

129
Q

Retinoids acid can be actively degraded into inactive metabolites by enzymes such as __

130
Q

Normally retinoids acid acts to __ the body plan

A

Posteriorize

131
Q

Excessive retinoids acid or inhibition of its degradation

A

Truncated body acid where structures have.a more posterior nature

132
Q

Insufficient retinoids acid or defects in enzymes (retinal eldehyde dehydrogenase)

A

More anteriorized structures

133
Q

Retinoids acid binds to receptors __ (transcription factors)the cell and their activation will regulate expression of downstream genes

134
Q

__ genes are a crucial target of retinoids acid receptors in development

135
Q

When are retinoids powerful teratogens

A

1st trimester

136
Q

Extrinsic signaling by ___ guides the differentiation and migration of cells during development , determining the morphology and function of developing tissues and organs

A

Morphogens

137
Q

Many morphogens rare found in __ __ int he embryo

A

Concentration gradients

138
Q

Cells can be attracted or repelled by morphogens depending on what

A

Receptor on the cell

139
Q

Different morphogens can be expressed in opposing gradients in the __ and ___ and ___ axes

A

Dorsoventral
Anteroposterior
Mediolateral

140
Q

Gap junctions permit what to go though

A

Ions and small molecules less than 1 I’d

141
Q

What is a connexon

A

6 connexin

142
Q

In early development gap junctions are usually ___. Why

A

Open permitting exchange of small molecules in a relatively large region

143
Q

As development proceeded GJIC is more ___ why

A

Restricted

Establish boundaries such as in the rhombohedra’s of the developing hindbrain

144
Q

Mutation in connexin Cx43

A

Atherosclerosis

145
Q

Cadherine

A

Critical for embryonic morphogenetic as they regulat separation of cell layers (endothelial and epidermal), cell migration, cell sorting, establishment of well defined boundaries, synaptic connections and in growth cones of neurons

146
Q

Cadherine mediate interaction between the cel and what

A

It’s extracellular milieu

-neighboring cells and extracellular matrix

147
Q

/Where is e cadherin? N cadherin?

A

Epithelial

Neural cells

148
Q

Describe the typical cadherin molecule

A

Large extracellular domain, a transmembrane domain and an intracellular tail

149
Q

Describe the cadherin extracellular domain

A

Has five extracellular repeats and has four ca binding sites

150
Q

Cadherine form __ that interact with cadherin __ in adjacent cells

A

Dimer diners

151
Q

Where are cadherine found

A

Adhering junctions -tigh barrier

152
Q

Via its intracellluar domain, cadherin binds to ___, __ and ___

A

P230-catenin, b catenin, and a catenin

153
Q

What do p120, bcatenin and a catenin do

A

Connect cadherin to the cytoskeleton

154
Q

When is e cadherin expression lost

A

As epithelial cells transition to mesenchymal (EMT)

155
Q

What is EMT required for

A

Formation of NCC during development and the Sam process occurs in tumor development

156
Q

What is a morphogen

A

Diffusable molecules that specify which cell type will be generated at a specific anatomical location
Also direct the migration of cells and their processes to their final destination

157
Q

Name some morphogens

A

Retinoids acid, transforming growth factor b, bmp, shh, wnt

158
Q

Characteristics of stem cells

A

Not terminally differentiated

Can divide without limit
Slow division

159
Q

What happens when stem cells divide

A

1 cell with stem cell characteristics and other can differentiate

160
Q

Adult stem cells

A

Tissue specific

161
Q

Zygote

A

Totipotent

162
Q

Embryonic stem cell

A

Pluripotent (blastocyst inner cell mass)

163
Q

Multipotent

A

Adult stem cell

164
Q

Founder stem cells

A

If the adult organ needs to be renewed, founder stem cells can divide as stem cells giving rise to one daughter cell that remains a stem cell and a set of cells that have a set number of transit amplifying divisions

Each tissue has fixed number of founder cell Polaroid. Programmed to have fixed number of divisions

Controlled by short range signals that operate for a few hundred cell diameter

Define size of large final structure

165
Q

Transit amplifying cells

A

Divide frequently

Transit from a cell with stem cell to a differentiated

Leave basal layer and incorporate into other

Programmed to have limited number of divisions
-Growth control

166
Q

How do we maintain stem cells

A

Divisional asymmetry-one is stem one can differentiate

Env asymmetry
-env may influence one cell after identical division

167
Q

Immortal strand

A

Some tissues stem cells retain original dna

Preserved ins them cells from generation to generation

Second cell gets new strand

168
Q

ESC risk if injected into adult

A

May become teratomas

169
Q

Teratoma

A

No axis formation or segmentation
Es incapable of generating the body plan

No organization in es

170
Q

How grow ES

A

Serum medium

Or serum free with serum replacement and FGF

171
Q

Two methods for getting patient specific cells

A

Induced pluripotent patient (iPSC)or non patient derived (iPSC ESC)

172
Q

Mesenchymal stem cell

A

Wharton jelly
Bone marrow
Adipose and tooth pulp

173
Q

Neural stem cell

A

Can repopulate CNS

174
Q

Induced pluripotent

A

After fertilization zygote undergoes equal divisions, totipotent. 4 days after become blastocysts. Inner cell mass is pluripotent

175
Q

Somatic cell nuclear transfer

A

Remove nucleus of egg cell, put somatic cell of any type in the egg cell. Stimulate cell division and get inner cell mass a pluripotent embryonic stem cell

-can make pancreatic stem cells for transplant in diabetic

Embryology (12 decks)

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