Dev Genetics, Stem Cells, Control of Differentiation, Hgb

Question 1

selector genes

Answer 1

originally identified in Drosophila, responsible for determining body segment identity
- Initiate cascade of gene expression events that leads to formation of particular structure or organ

Question 2

Hox genes

Answer 2

• specify developmental fate of a specific body region by providing cells with permanent record of original location within early embryo
• low numbered : left streak first

Question 3

Hox cluster

Answer 3

1 in Drosophila, duplicated twice –> 4 clusters in humans (A-D located on four different chromosomes)

Question 4

induction

Answer 4

signal from one cell or group of cells influences development of another

Question 5

competence

Answer 5

cells that can respond to extracellular signal because they express necessary receptor protein

Question 6

Signaling system that direct embryonic development

Answer 6

SHH, TGFB, EGF/FGF, WNT, RA

Question 7

FGF receptor mutations leads to…

Answer 7

1. achondroplasia

2. craniosynostosis

Question 8

HOXD13 gene mutation

Answer 8

polysyndactyly

Question 9

Shh gene mutation

Answer 9

holoprosencephaly (hypo-/hypertelorism)

Question 10

RA embryopathy

Answer 10

• Rhombomeres will form hindbrain
• Rhombomeres have Hox genes with RAREs, tightly regulated by RA

Pattern: craniofacial, cardiac, thymic, CNS, hindbrain most affected, reduced mental ability
40% rate spontaneous abortion, 35% malformation

Question 11

Characteristics of stem cell

Answer 11

self-renewal, potency

toti: all
pluri: not extraembryonic
multi: organ-specific
oligo: only few cell types

Question 12

PAX2 gene mutation

Answer 12

Renal-Coloboma Syndrome
colobomas, clefting defects of eye
Underdevelopment of kidneys

Question 13

stem cell population in skin

Answer 13

basal epidermis layer

Question 14

stem cell population in small intestine

Answer 14

crypt base columnar stem cells in intestinal crypt

Question 15

TACs

Answer 15

transit amplifying cells

• committed progenitors between adult stem cells and all their terminally differentiated daughter cells
• allows one committed cell to produce many terminally differentiated cells

Question 16

genomic equivalence

Answer 16

• proven by ability to clone whole animal from single somatic cell
• Gurdon xenopus experiments

Question 17

mosaic/determinative

Answer 17

cell division precisely defined, loss of any individual cell leads to defective final structure

Question 18

regulative/flexible

Answer 18

each cell division not precisely defined, cells have multiple potential fates

Question 19

cell fate

Answer 19

what cell would become if allowed to continue through unperturbed environment

Question 20

cell determination

Answer 20

progressive restriction of cellular potential during development

Question 21

cell differentiation

Answer 21

irreversible change in cellular specialization, distinct cellular phenotype

Question 22

autonomous determination

Answer 22

produces mosaic/determinative development pattern (so tissues cannot compensate for loss of cells)

Question 23

conditional determination

Answer 23

• interactions between cells or groups of cells causes differential determination
• produces regulative/flexible development pattern

Question 24

syncytial determination

Answer 24

many nuclei in same cytoplasm (insects)

Question 25

regionally specific induction

Answer 25

distinct regional inductive signals induce competent cell to produce distinct type

i.e. same type of epithelium forms different structures depending on underlying mesenchyme

Question 26

genetically specific induction

Answer 26

responding group of cells can only comply with instructions as far as genome permits

i.e. can move presumptive mouth graft to another organism, but will only form mouth of donor organism

Question 27

paracrine sinaling

Answer 27

works locally

Question 28

juxtacrine signaling

Answer 28

cells directly touch

Question 29

Examples of paracrine signaling

Answer 29

Shh, Wnt, TGF, FGF

Question 30

Examples of juxtacrine signaling

Answer 30

integrin/ECM, Notch (important in nervous system), gap junctions

Question 31

Hb structure

Answer 31

tetramer (two alpha two beta) held by non-covalent bonds

each subunit contains heme that can each bind an O2

Question 32

Hb O2 equilibrium curve

Answer 32

Hb allows for changes in Hb saturation and O2 concentration without big flux of partial pressure of O2

Question 33

Cooperativity of O2 binding to Hb

Answer 33

O2 binding to Hb increases Hb affinity for O2

Question 34

Shape of Mb and Hb curves

Answer 34

rectangular hyperbolic, classic sigmoidal “S” shaped

rectangular hyperbolic shows that Hb is allosterically regulated

Question 35

Negative regulators of O2 binding to Hb

Answer 35

• let’s go of O2 easier, curve shift right
• CO2: stabilizes T conformation (accounts for 15% CO2 transport in blood)
• decreased pH
• metabolically active tissues
• increased BPG (high altitude): stabilize T conform
• anemia

Question 36

Positive regulators of O2 binding to Hb

Answer 36

• hold tight to O2, curve shift left
• CO: stabilizes R state, takes up O2 but can’t release
• increased pH
• HbF
• decreased BPG

Question 37

Bohr Effect

Answer 37

Positive charges (decreased pH) allows for formation of salt bridges that stabilize deoxy T form

Question 38

HbF

Answer 38

• binds BPG weakly, higher affinity for O2, curve shifted left

Question 39

Mb

Answer 39

one globin subunit, one heme, one O2

Higher affinity