Cell Bio Part 3- Developmental Cell Bio (Complete)

Front 1

What are the things that are different in cells? (3)

Back 1

-protein expression;
-environment;
-differentiation;

Genome is the same in all cells, except immune cells- no nucleus

Front 2

What is combinatorial control?

Back 2

Most genes are controlled by a specific combination of regulatory factors that promote and repress gene expression

Front 3

Chromatin accessibility

Back 3

The state of chromatins that impacts transcription factor binding to DNA and transcriptional specificity. Differences in this diversifies cells

Front 4

Cell Fate

Back 4

The differentiated cell type the cell will become. As cells divide, they become less totipotent and cell fate is progressively restricted. Patterns of gene expression changes, signal receptors change, so the cell can only respond to certain signals. This is regulated by transcriptional control.

Front 5

Housekeeping gene

Back 5

A gene expressed in every cell- used as a control to compare to genes that only specific cells express

Front 6

What are the two ways to transition between cell states?

Back 6

(1) extrinsic cues- cell signals;
(2) intrinsic cues- segregation of determinants- determinants go to one side of the cell so when the cell divides only one daughter cell has determinant

Front 7

What do morphogens do?

Back 7

Morphogens are cell signals that cells react to based on where they are in the morphogen gradient. Can cause cells to differentiate into different cell types based on how much of the morphogen is present.

Front 8

Morphogens in the neural tube

Back 8

Shh and BMP are neural morphogens in opposing gradients which induce expression of specific transcription factors to pattern motor neuron subtype in the developing neural tube.

Front 9

Lateral Inhibition

Back 9

Type of cell-cell signaling; both cells initially have the same amount of X (stable state 1) and have equal potential of becoming one type of cell or another type of cell, until one randomly expresses a little more, then there's positive feedback where the cell with more gets signals to produce more and the cell with less gets signals to produce less until there is one cell with all of X and another with none (stable state 2)

Front 10

Lateral inhibition in C. Elegans

Back 10

Cells Z1.ppp & Z4.aaa can make AC or VU type cells, wild type always has one of each. They're always neighbors. Killing either one of them with laser causes the other one become AC, AC is default. lin-12 null mutants- both cells AC. lin-12 gain of function or lag-2 null mutants- both cells VU. lag-2 (delta) required for VU; lin-12(notch) required for AC

Front 11

What is a determinant?

Back 11

A factor that is both necessary and sufficient to specify a particular cell fate

Front 12

What must occur for cell division to be asymmetric? (2)

Back 12

(1) Cytoplasmic or membrane components must be localized to (or enriched in) one side of the cell
(2) The mitotic spindle must be oriented such that the localized components are preferentially segregated to one daughter cell over the other

Front 13

Advantages of using nematode C. elegans for developmental bio studies

Back 13

Short life cycle, simple anatomy, transparent at all stages, fully defined cell lineage, conserved developmental pathways, genetically tractable

Front 14

How is embryonic asymmetry generated?

Back 14

Front 15

C elegans embryo division & determinant

Back 15

P0 parent cell divides into P1 (posterior side) and AB (anterior side). PIE-1 is a determinant that specifies the P1 line of cells, and if there is any PIE-1 left in AB, it gets degraded.

Front 16

What controls asymmetric cell division? How was this discovered?

Back 16

PAR family; PAR mutants only have symmetrical cell division. Different PAR proteins localize in different areas of the cell by reciprocal inhibition to define two different domains for asymmetric cell division. This was discovered by using a genetic approach by creating mutants and looking for ones where the asymmetry is lost.

Front 17

What provides the initial symmetry-breaking cue?

Back 17

The site of sperm entry defines posterior side-- it stops cortical streaming on that side of the cell.

Front 18

What is the pathway that initiates/stops cortical actin contractility (cortical streaming)?

Back 18

cortical streaming helps push PAR-3, PAR-6 to the anterior side and set up cell assymetry. To make cell streaming direction, it is shut off at the posterior side. This happens by regulating Rho-1 spacially.

Front 19

What generates the force that moves the spindle?

Back 19

Microtubules, because when you break the mitotic spindle with a laser, the nuclei are pushed farther away from each other because there's no force holding them together.

Front 20

Why is there a greater pulling force on the posterior side?

Back 20

There are more dynein complexes on the posterior side which pull the microtubules attached the nucleus closer compared to the anterior side.

Front 21

What are the mechanisms for the segregation of determinants? (3)

Back 21

(1) Protein segregation
(2) Differential protein stability
(3) mRNA segregation

Front 22

Drosophila sensory organ development

Back 22

pI is the SOP (sensory organ precursor cell) which divides asymmetrically into pIIa and pIIb. pIIa gives rise to external components, pIIb gives rise to internal components

Front 23

What does Notch signaling do?

Back 23

High notch signals to pIIa, and low notch signaling to pIIb. Hyperactive notch signaling transforms pIIb to pIIa. This is not lateral inhibition because numb in pIIb forces it to have low notch.

Front 24

What does numb do?

Back 24

It's a determinant for pIIb fate; mutants deficient of numb only have pIIa, numb overexpression leads to 2 pIIb daughter cells. Numb asymmetry depends on Par3/Par6. Numb also downregulates Notch signaling by degrading Spdo (notch cofactor).

Front 25

2 approaches for identifying determinants

Back 25

(1) Molecular/cellular approach- look for a factor that can trigger differentiation of precursor cells in vitro
(2) Genetic approach: look for mutants that fail to make a particular cell type

Front 26

How was MyoD identified?

Back 26

Using a molecular approach. Fibroblasts, which don't usually make muscle cells, treated with 5-azacC turned into myotubes. mRNA was isolated from myotubes, total cDNA was prepared, then split up and transfected into fibroblasts, and some became myotubes. Therefore, myoD is sufficient to transform fibroblasts into myotubes. MyoD is a basic-helix-loop-helix transcription factor that transcribes muscle specific genes

Front 27

Is myoD necessary for muscle cell development?

Back 27

No, MyoD knockout mice still had muscles. Turns out there is a family: MyoD, MyoG, Myf5,Mrf4, which are determinants for muscle cells as a family. If all are knocked out. If just one is knocked out, there are still muscles because others can make muscles.

Front 28

What is the determinant for eye development?

Back 28

Eyeless (in drosphila); Pax6 in mammals. It encodes a paired-HD family transcription factor. It's necessary for eye development because eyeless mutant has no eyes. Eyeless expression is sufficient because when expressed on the leg of a fly, eye begins to form there. This is a genetic approach for finding a determinant