Embryo Molec 2

Question 1

What is the concept of Gene “even-skiped”

Answer 1

The promoter of a gene can recognize different molecules. As such, depending on the promoter factors, the system can express a lot or little of the given gene. (or none)

The mix of molecules that activate and deactivate the promoter will decide the concentration of the gene in the cell. This concept applies to many promoteur regions and genes.

Question 2

Que cause une mutation de gène homéotique?

Answer 2

The mutation of a homéotique gene leads to the differentiation of one segment to another.

ex., chez la drosophile, une mutation du gène antennapedia faït que les antennes sont remplacées par des pattes

Question 3

Que contiennent les homéoprotéines?

Answer 3

There are 2 types of homeotic genes:

1. 60 amino acid sequence is conserved
2. Genes that are on a complex → GENES HOX
   
   1. Hox literally just means that homeotic genes are on a complex

Question 4

Vrai ou faux? Les gènes dérivés d’un même gène primordial sont moins homologue moléculairement qu’avec les gènes HOX de leur même complexe.

Ex: HOXA2 est plus homologue avec HOXA3 qu’avec HOXB2

Answer 4

Faux

Question 5

Qu’est-ce qui joue un rôle majeur dans l’expression spatiale et chronologique des HOX?

Answer 5

Acide rétinoique

Question 6

Dans quel axe sépare HOX?

Answer 6

Caudo-céphalique

Question 7

Est-ce que l’action des HOX A4, B4, C4 et D4 sont interchangeable?

Answer 7

Oui (grande redondance)
assurence

Question 8

Quel gène contrôleur maitre est diffusé par le tube neural dorsal?

Answer 8

BPM

Question 9

Par qui est segmentée le tube neural dorso-ventralement?

Answer 9

SHH
BPM

Question 10

Décrit la segmentation de l’arbre broncho-alvéolaire.

Answer 10

• FGF10 secretion and cell proliferation: A group of mesenchymal cells secretes FGF10, which diffuses and stimulates cell proliferation at the tip of the epithelial bud (A).
• SHH secretion and FGF10 inhibition: FGF10 stimulates the secretion of SHH by these epithelial cells.
  
  • SHH diffuses and inhibits the synthesis of FGF10 by the mesenchymal cells exposed to a high concentration of SHH. The aggregate of mesenchymal cells is thus split into two independent aggregates (B).
• Epithelial bud branching: Each of the aggregates of mesenchymal cells independently stimulates cell proliferation at the tip of the epithelial bud, which thus divides into two branches (C).
• Cycle repetition: The cycle repeats: as in A), FGF10 stimulates each of the new branches to grow and secrete SHH.

Question 11

What are SHH and BMP proteins

Answer 11

both morphogens (by definition activating master control genes), plays a crucial role in the dorso-ventral segmentation of the embryo.

Question 12

Production go SHH and BMP

Answer 12

proteins are produced by the ventral notochord (SHH) and the dorsal cells (BMP) of the neural tube, respectively. (name of molecules is irrelevant)

Question 13

Que cause une mutation de HOXD13?

Answer 13

Syndatylie
Polydactylie

Question 14

What is a Helice-Boucle-Helice:

Answer 14

Facteur de Transcription

Bind to DNA and can activate or inactivate different promotors

If we hear helices-boucle helices → 🛎️ Transcription Factor, change in DNA conformation, euchromatin or heterochromatin, accessible or not , transcription or inhibition

Question 15

Why is inhibition of a gene as important and activation?

Answer 15

The importance of being able to inhibit is that when you want say your muscle cell to be a muscle, well you also don’t want it to be a neuron.

Question 16

Describe PAX Genes:

Answer 16

• transcription factors.
• Also very conserved in evolution.
• Can trigger the creation of a specific region.
• A combination of PAX genes that bind to promoter regions can have different effects based on their combination in epithelial and mesenchyme expression.

We do not know exactly how they work, but we know that they can determine the structure development of certain regions

Question 17

Role of PAX-6?

Answer 17

PAX-6 is responsible for triggering the entire molecular cascade necessary for eye development.

2. The expression of PAX-6 is a sine qua non condition for eye development: without this expression, the eye does not even form a rudiment.
3. Moreover, an ectopic expression of PAX-6 is sufficient for the complete and perfect formation of an eye where this expression occurs.

Question 18

hetero vs homo for lack of PAX-6?

Answer 18

4. In humans, a deficiency in PAX- 6 can lead to malformed eyes.
   
   1. If heterozygous : small eyes
   2. If homozygote: no eyes at all

Question 19

Lack of SHH with normal expression of PAX-6?

Answer 19

5. Just like we need PAX-6 to make an eye we need SHH in order to form 2 eyes.
   
   1. SHH plays a key role in differentiating the region where NO EYES should form. I.e., inhibits eye formation. This separates the region into eye-forming ; SHH; eye-forming and thus we have 2 eyes.

Question 20

What are zinc-finger genes?

Answer 20

• transcription factor.
• They code for proteins whose three-dimensional structure resembles fingers (thanks to zinc molecules).
• The amino acids of these proteins bind to the promoters of the genes they control, in order to activate or inhibit these promoters.

They integrate in the DNA and change confirmation to activate or inhibit.

Question 21

Explique les exosomes.

Answer 21

Exosomes are micro-vesicles of 30 to 100 nm in diameter that contain proteins, mRNA and miRNA.

Les cellules peuvent moduler leurs voisines et des cellules distantes par la sécrétion d’exosomes

Question 22

True or Flase,

différents types de cellules peuvent exprimer différents types de récepteurs qui réagissent au même ligand

Answer 22

True

Question 23

Netrins and Sémaphores:

Answer 23

Netrins:

Chemoattraction molecules

Sémaphores:

Red light → chemo repulsion molecules

These signals are key in neuronal and axonal proliferation especially important in axonal decussation at the medulla of the spinal cord.

Another great example is the optic chiasm.

Question 24

Describe the concept of Combinatorial Response:

Answer 24

combined action of a variety of stimuli can have a specific response on a cell and that the SAME signal can have different effect DEPENDING ON THE CELL. Almost like a code.

Différents types de cellules peuvent exprimer différents types de récepteurs qui reconnaissent néanmoins les mêmes ligands;
Un récepteur peut activer différentes cascades moléculaires, dépendamment du type de cellules qui l’expriment: un récepteur peut interagir (c. à d., être couplé) avec différentes molécules cytoplasmiques, et la différenciation contrôle l’activité des molécules / cascades de cette cellule.

For example, a combination of factors can lead to differentiation of a cell. A lack of any signaling can lead to apoptosis.

Dépendamment des récepteurs exprimés par une cellule et des signaux auxquels cette cellule est exposée.

Question 25

Exosomes have a crucial physiological role, both in embryonic development and in adults. What is their role in cancer?

Answer 25

- **Cancers can produce exosomes that can send signals that can inform us if a cancer is developing or not.** - Great way to see if a cancer is going to métastasé to other tissues.

Question 26

Exosomes and role in implantation

Answer 26

One of the key steps of implantation in the endometrium requires communication between the mother and the embryo via exosomes that establish for example necessary receptors that will tell the mother’s cells that the embryo is not **immunologically dangerous. ** During implantation, more than 500 different miRNAs are produced by the embryo and the female genital tract, allowing essential cross-talk between the mother and the embryo / fetus. This communication is local (paracrine) but also distant via the transport of exosomes in the maternal blood circulation.

Question 27

Describe Inhibition lateral

Answer 27

Initially similar cells all try to inhibit their neighbors. B) The cells that resist inhibition better (in orange; just by chance) express a **transcription factor** that induces the **synthesis of an inhibitor** (illustrated as T) and decreases the synthesis of the receptor for this inhibitor; *Let's make more inhibitor and let’s become resistant to the inhibitor.* This inhibitor prevents the production of the transcription factor (FT) in the neighboring cells, thus reducing the inhibition to which the inhibitory cells are subjected. FT also triggers the formation of the hair / feather follicle.

Question 28

Par quoi est accomplie la segmentation g/d?

Answer 28

Par le battement des cils du noeud de Hensen qui distribue les morphogènes de façon asymétrique

Question 29

Localisation de le première paire de somites?

Answer 29

Région cervicale Cervical vers caudal

Question 30

Vrai ou faux? Chaque somite induit la formation de la prochaine.

Answer 30

Vrai

Question 31

Décrit le développement selon l’horloge moléculaire ## Footnote FGF8, WNT3a, AXIN, NOTCH

Answer 31

- **FGF8 and WNT3a production**: The protein FGF8 is produced constantly. **(a) In the absence of the protein AXIN, FGF8 stimulates the production of WNT3a.** (b) **WNT3a activates the NOTCH cascade, to trigger a molecular cascade.** **WNT3a also stimulates the promoter of AXIN with production of the protein AXIN** that inhibits the promoter of WNT3a. - **AXIN half-life and WNT3a inhibition**: (d) Assuming AXIN has a half-life of 90 minutes, the production of WNT3a will be inhibited for about an hour; (e) then, in the absence of the protein AXIN, (f) the protein WNT3a will start to be produced again. - **Gene and protein notation: Note that by convention, when the name is written in italics, it designates the gene. The protein is indicated by normal characters. In addition, human genes and proteins are designated by writing all the letters in uppercase.** - Here, each cycle of FGF8 WNT3a will make 1 somite.

Question 32

Quand se développent les espaces centraux des somites?

Answer 32

Quand NOTCH est au plus fort

Question 33

Chemoreceptor Function loss and problem

Answer 33

They have membrane receptors that can sense specific chemicals and trigger an appropriate cascade One of those receptors is a **SHH** receptor → if you have no cils then your **SHH signaling can be affected** ## Footnote Meckel-Gruber

Question 34

Cause du syndrome de Meckel-Gruber?

Answer 34

Anomalie des cils

Question 35

Que permet la fonction mécanoréceptrice des cils?

Answer 35

Cilia can come out of cells and sense for example a flow of air or liquid. This movement leads to the opening of calcium channels which is read by the cell. This signal can be used for example in the kidney to determine the right angle for splitting. Example, the angle at which the cilia is found can determine centriole positioning and thus mitotic splitting. Without cilia the splitting of the cells might be random and unorganized leading to cysts. | Permettre de bien polariser certains tubules (orienter les cellules)

Question 36

Mode de transmission du syndrome de Meckel-Gruber?

Answer 36

Autosomique récessive

Question 37

Vrai ou faux? Les ciliopathies sont toutes à risque de développer une anomalie de segmentation.

Answer 37

Vrai

Question 38

Explain Syndrome de Meckel-Gruber:

Answer 38

Pathology des cils 1. The cilia anomaly in this syndrome causes cranial rachischisis with exencephaly, polydactyly of the hands and feet. 2. There is an anomaly of the hepatic and pancreatic tubules - they fill with secretions, causing peritubular fibrosis. 3. The kidneys become enormous. 4. Renal tubules are depolarized and become cystic. 5. They cannot excrete urine into the ureters, and the ureters and bladder are very hypoplastic since there is no urinary flow in these structures. 6. The absence of urine causes oligohydramnios or a total absence of amniotic fluid (anamnios). 7. The fetus is therefore crushed by the uterus, and its limbs cannot move (this movement is essential for the development of the joints. Without movement, the joints are fused - arthrogryposis). 8. The fetal lungs must “breathe” their amniotic fluid to grow normally. 9. Oligohydramnios causes a **Potter sequence**, with very severe pulmonary hypoplasia and rapidly fatal.