14.3 Cell Differentiation II

Question 1

What are the three major body parts of the fruit fly (drosophila melanogaster)?

Answer 1

Head
Thorax
Abdomen

Question 2

How do each major body part of the fruit fly develop?

Answer 2

as a result of genes expressed in the developing embryo

Question 3

How many segments are in the head, thorax, and abdomen of a fruit fly?

Answer 3

Head - four segments

Thorax- three segments, each will produce one pair of legs (total of 6 legs)

Abdomen- has 8-9 segments

Question 4

How early genes that establish the development of each segment in fruit fly be detected?

Answer 4

in the embryo, as early as 5 hours after fertilization of the egg.

Question 5

How do appendages and other accessory structures that are present in the adult fly develop?

Answer 5

from specialized tissues that are produced in the embryo called imaginable discs.

Although imaginable discs are not easily seen in the embryo and larvae (b/c their inside the animal) their development is also regulated by genes that are expressed in early development.

Question 6

The fruit fly embryo hatches into…

Answer 6

a larva aka maggot.

Question 7

How is the segmented nature of the embryo seen on larva?

Answer 7

seen by the presence of ridges of hardened scale-like epidermal protrusions which help the animal get traction as it crawls.

Question 8

Epidermal ridges are found on which side of the larva?

Answer 8

only on one side and that is the ventral or bottom side.

Question 9

What generates the overall body plan of the drosophila embryo?

Answer 9

the body plan is generated by the expression of a set of genes called egg polarity genes.

There are three genes that generate the anterior and posterior axis of the embryo and one that generates the dorso-ventral axis.

Question 10

What genes generate the anterior and posterior axis?

Answer 10

genes called Bicoid, which is found in the head or anterior and Nanos, which is expresses in the tail or posterior regions of the embryo.

Question 11

The very ends of the larva are defined by the expression of what terminal gene?

Answer 11

terminal gene called torso.

Question 12

What happens if the terminal gene torso is inactivated?

Answer 12

the embryo develops but lacks head and tail structures.

Question 13

What gene generates the dorso-ventral system?

Answer 13

controlled b the expression of the gene Toll, which is produced in the ventral half of the animal.

Question 14

What type of gene is Toll and what occurs when it is activated?

Answer 14

Toll is a transmembrane receptor and its activation leads to the expression of several other genes involved in determining the dorso-ventral axis of the embryo.

Toll is also a member of the NFkB signaling receptors

Question 15

Where are Bicoid, Nanos, Torso, and Toll produced?

Answer 15

These four egg polarity genes are produced in the egg in a predetermined pattern during the development of the egg w/in the female fly. Therefore these genes are called maternal effect genes.

Question 16

List the maternal effect genes:

Answer 16

Bicoid: anterior axis
Nanos: posterior axis
Torso: very end of the animal
Toll: dorso-posterior axis

Question 17

How is the egg polarity of the drosophila egg programmed?

Answer 17

by the female drosophila

Question 18

How is the polarity determination of a drosophila different than that of C elegans?

Answer 18

In drosophila it is determined by the female and in C elegans polarity of the embryo is determined by the site of sperm entry.

Question 19

How have the roles of egg polarity genes been established?

Answer 19

through mutagens studies.

Question 20

What is the protein Dorsal?

Answer 20

the downstream activated gene regulator that enters the nucleus of the cell when Toll is activated (reminder Toll is a member of the NFkB signaling receptors)

Question 21

How is Toll expressed in the embryo? How is it activated?

Answer 21

Toll is expressed uniformly on the surface of the embryo

it is activated by factors secreted by surrounding maternal cels found only on the side of the embryo

Question 22

Where does Dorsal protein enter the nucleus of cells?

Answer 22

at the bottom or ventral surface of the embryo. Cells at the top or dorsal surface show no nuclear entry of Dorsal and cells in between show a gradation from the top to bottom.

Question 23

What occurs when Dorsal enters the nucleus? What about in the absence of Dorsal?

Answer 23

it drives expression of genes found in the ventral side of the embryo including a protein called Twist.

The absence of Dorsal allows expression of other genes in the dorsal side of the embryo including one called decapentaplegic.

Question 24

What occurs if there’s a mutation in dentapentaplegic? What side is this gene found?

Answer 24

Mutation results in the loss of all 15 appendage structures derived from imaginable discs.

found on dorsal side

Question 25

how do cells that have an intermediate amount of activated dorsal behave?

Answer 25

they will generate another regulatory factor called short gastrulation or Sog.

Question 26

What occurs (what do they become) with the Twist expressing cells in embryos?

Answer 26

these cells invaginate during development and become mesodermal structures such as the heart and other muscles.

Question 27

What occurs if decapentaplegic is disabled?

Answer 27

the signal to generate a dorsal surface is not generated. Therefore the epidermal ridges which are normally restricted to the ventral surface of the embryo extend around the entire body.

Question 28

How are the genes involved in producing dorsal and ventral structures conserved in insects and vertebrates??

Answer 28

In the fly or other insects the circulatory system is found on the dorsal side of the animal and the nervous system develops on the ventral side.

In vertebrates, this program is reversed. Circulatory found on ventral side and nervous system found on dorsal.

Therefore, at some point, one of these organism flipped the way it interprets the dorso ventral axis.

Question 29

What must occur first in the embryo before developmental regulations are involved in defining the patter of segments?

Answer 29

the main axes of the body plan need to be established.

Question 30

The body plan of the embryo is set up by?

Answer 30

a progression of regulatory genes whose activities result in progressively finer distinctions between different parts of the embryo.

Question 31

What are gap genes? What are examples of gap genes?

Answer 31

Gap genes play a role in defining the pattern of segments. They outline relatively large segments of the embryo although these regions are more refined that the ones produced by egg polarity genes.

Examples of gap genes are Kruppell and Hunchback

Question 32

Loss of the gap gene Kruppell results in?

Answer 32

in an embryo that lacks the thorax and four of the abdominal segments. However, the rest of the embryo will be relatively normal.

Question 33

What follows in development after the expression of gap genes (to outline large segments of the embryo)? What are examples of these genes?

Answer 33

following the expression of gap genes are a group of regulatory elements called pair-ruled genes. These will become expressed.

Examples: Even skipped and Fushi Tarazu abbreviated Ttz. Each of these genes become activated in every other segment of the body. For example, normal embryos have 9 abdominal segments, but embryos that are mutate for the function of even skipped have only 5 and are missing segments 1, 3, 5, and 7.

Question 34

Which group of genes establishes a gradient across segments and defines the anterior and posterior of each segment?

Answer 34

These genes are called segments polarity genes and an example is the gene gooseberry.

There are at least 10 different segment polarity genes.

Question 35

Loss of function in gooseberry results in?

Answer 35

an embryo where the anterior of each segment is duplicated in the posterior.

Question 36

How are the expression of developmental control genes that appear over and over again in the body regulated?

Answer 36

The gene for even skipped as a single coding region and there is only one gene. The regulatory DNA found on either side of the coding sequence called the gene promoter has complex regulatory elements that drive expression under many different conditions.

Development occur in a modular fashion. Modular control of gene expression allows the genome to be much smaller then it would have to be if every part of the body required its own set of genes in order to develop.

Question 37

What does transient expression of developmental genes create?

Answer 37

permanent changes in cells and tissue

Question 38

How are early developmental regulators expressed?

Answer 38

transiently; they changes they make in tissue are permanent.

Ex: early genes lead to segment specific expression of a gene regulator called engrailed. Engrailed is a segment polarity gene. the expression of engrailed is part of the system that maintains cells and tissues in a differentiated state through the life of the organism.

Question 39

What is the sensory bristle on the fruit fly?

Answer 39

a structure that is useful model for the development of more complicated structures, because the bristle has only four cells.

Question 40

What are the four cells of a sensory bristle?

Answer 40

one cell is a nerve cell that transmits a signal if the bristles toughed by something

The other three cells create the structure of the bristle (sheath cell)itself and of two accessory supporting structures (shaft cell and socket cell)

Question 41

How does the bristle develop?

Answer 41

from a single cell called the sensory mother cell, which itself develops w/in the imaginable discs of the larva.

Question 42

What genes in imaginable disc produce sensory bristle?

Answer 42

the expression of the genes Scute and Achaete

These are proneural genes and their expression prepares all cells for the process of becoming nerves. However, the density of each of these cells is further refined so that only one cell in each of the developing bristle becomes a nerve cell.

Question 43

Only a few of the cells in the imaginal disc develop into sensory mother cells and give rise to bristles, while all of the others become epithelial cells. What mechanism controls this?

Answer 43

Sensory neurons uses the delta/notch signaling system.

A cell which will become a sensory mother cell in the developing imaginal disc signals its neighbors by producing delta on its surface. This activates notch receptors on its neighbors. The result of activating notch is to cause specialization of the cell into epithelial cells and also leads down regulation of the expression of delta. The down regulation of delta can be considered a negative feedback loop so that w/in a short time the initial cell is the only one expressing delta and the surrounding cells are the only ones that have activated notches.

Question 44

What happens in drosophila if delta has been inactivated in all cells?

Answer 44

since none of the cells in the region receive the signal to turn off neurogenic development all of them become sensory mother cells and then bristles. The result is a patch of epidermal tissue with a very dense cluster of bristles that is easily seen on the mutagenesis screen.

Question 45

Explain how sensory mother cell instructs neighboring cells in the developing disc

Answer 45

it instructs the developing imaginal disc to become epithelial cell instead of sensory mother cell divides twice to produce enough cells to form the bristle and only one of the final cells becomes the neuron. At each cell division only one cell retains the ability to become the nerve cell and the others go on to other fates.

Question 46

What is the role of the protein Numb?

Answer 46

numb is produces in the initial sensory mother cell. Numb becomes localized to only on end of the dividing cell and it is therefore inherited by only one daughter cell at each cell division. The activity of numb makes a cell resistant to notch signaling so the cell that expresses Numb doesn’t receive notch signals from its neighbors therefore the cell will act like the cells in the patch of bristles on a mutant fly.

Similar to P-granules on development of C elegans.

Question 47

Summary of the events that lead to sensory bristle development in Drosophila:

Answer 47

-Expression of proneural genes is transient-only a minority of cells expressing
these genes will go on to become sensory mother cells-rest will become
epidermis.
 Each “sensory mother cell” is surrounded by cells that switch off expression of proneural genes and differentiate as epidermis.
 Lateral inhibition singles out sensory mother cells
- Cells expressing proneural genes undergo competitive lateral inhibition
- As a result, a single cell in a group becomes the “sensory mother cell” and
express proneural genes; other cells do not.
- The cell that ultimately becomes the “sensory mother cell” sends a signal to its neighbors to switch off expression of proneural genes, via a mechanism
called lateral inhibition.
- Lateral inhibitions mediated by Notch signaling pathway.
- Cells initially all express Notch and its ligand Delta. Wherever
 Delta activates Notch, an inhibitor signal is sent into Notch-expressing cell; so all cells in cluster initially inhibit each other.
- Receipt of inhibitory signal reduces its ability to deliver inhibitory Delta
signal.