Basic Developmental Biology Deck 1

Question 1

What are the 7 major inductive signaling pathways in development? Break them down into long range and short range.

Answer 1

Long range: SHH, BMP/TGFbeta, Wnt, FGF, Retinoic acid

Short range: Notch/Delta, Eph/ephrin

Question 2

What are homeotic genes?

Answer 2

genes which regulate the development of anatomical structures. Mutations in homeotic genes can lead to ectopic placement of body parts (eg. legs for antennae).

Question 3

What does ectoderm give rise to?

Answer 3

epidermis, nervous system, meninges, skin, mammary gland, pituitary gland, adrenal medulla.

Question 4

What does mesoderm give rise to?

Answer 4

muscle, bone, connective tissue, heart, kidney, gonad, vascular and lympathic vessels, adrenal cortex, lining of the body cavities.

Question 5

What does endoderm give rise to?

Answer 5

lining of gut, lungs, liver, pancreas, urinary tracts, thyroid and parathyroid glands.

Question 6

What two types of cells does the blastocyst give rise to and what TFs cause the differentiation?

Answer 6

1) trophectoderm / trophoblast (cdx2, synthesized due to lack of hippo signal because lack of cell-cell adhesion, Yap enters nucleus, binds Tead4, turns on cdx2).
2) inner cell mass (oct4, cell-cell adhesion turns on hippo pathway, Yap phosphorylated, doesn’t enter nucleus, no cdx2, Oct 4 instead.

Question 7

What types of cells does the inner cell mass give rise to and what TFs cause the differentiation?

Answer 7

1) Hypoblast = primitive endoderm, Gata6 (primarily produces cells of the yoke sac and amnion)
2) epiblast = primative ectoderm, Nanog. (generates all cells of fetus)

Question 8

How does hedgehog pathway work?

Answer 8

In absence of Shh, the receptor Ptch1 inhibits Smo, Gli 1,2,3, which are TFs, don’t do much (Gli 1 not expressed, Gli2 degraded, Gli3 cleaved to repressor form).
In presence of Shh, the receptor Ptch1 is inhibited, Smo is active, Gli1,2,3 up regulate many genes.

Question 9

How does TGF-beta/BMP pathway work?

Answer 9

large family of ligands, serine/threonine protein kinases, ligand binds, activates Smad, Smad-cosmad dimer enter nucleus, alter gene expression.

Question 10

How does FGF signaling pathway work?

Answer 10

Large family of ligands, 4 receptors, tyrosine kinase receptors, FGF + hasp activates receptor, which activates Ras, causes phosphorylation cascade Mek/Erk pathway.

Question 11

How does Retinoic Acid signaling pathway work?

Answer 11

Precursor Vitamin A = retinol, activated, enters cell (hydrophobic molecule), enters nucleus, affects translation by witching RAR/RXR from repressors to activators.

Question 12

How does Eph/ephrin signaling pathway work?

Answer 12

bidirectional signaling involving GPI-linked “ligands” and transmembrane “ligands,” a la Delta/Notch signaling.

Question 13

What do the segments of the mesoderm become?

Answer 13

condensation of axial mesoderm -> notochord.
paraxial mesoderm -> somites
intermediate mesoderm -> GU system
lateral mesoderm -> two layers, top (next to ectoderm) becomes body wall and limbs. boom, next to endoderm, becomes visceral wall around gut. Space between these two layers gives rise to body cavities.

Question 14

What is the name of the space between the two sections of lateral mesoderm?

Answer 14

intraembryonic coelom, gives rise to blood islands and heart.

Question 15

What are the three structures in the fetus that allows the blood supply to (mostly) bypass the liver and lungs?

Answer 15

ductus venosus: connects umbilical blood supply to inferior vena cava, skipping liver.
foramen ovale: lets blood go from right atria to left atria, skipping blood supply to lungs.
ductus arteriosus: connects pulmonary artery to aorta, lets blood skip lungs.

Question 16

What is the zona pellucida?

Answer 16

glycoprotein coat surrounding the oocyte, which also contains cumulus cells. This is the zone sperm must cross, once they are ‘capacitated,’ to make it to the egg.

Question 17

What is compaction?

Answer 17

Process of increased adhesion of cells generating inside and outside cells, occurs at the 16 cell stage in humans, only a few of these cells become epiblast cells.

Question 18

What do trophoblastic cells become?

Answer 18

placenta - generate syncytiotrophoblast external layer and cytotrophoblast internal layer.

Question 19

How does the ligand Nodal act as a morphogen?

Answer 19

Nodal acts by binding activin with cripto as a co-receptor. The pathway is serine/threonine kinase, the transcription factor binds foxH1 turns on Nodal transcription and Lefty transcription, which inhibits Nodal, so as nodal diffuses, it is also inhibited by lefty, eliciting a dose depending signaling mechanism. Lefty acts at a longer range than Nodal.

Question 20

What is heterotaxia?

Answer 20

Randomized organ position involving many organs

Question 21

What is isomerism?

Answer 21

mirror image of single organs.

Question 22

What signaling pathways are important in AP axis distinction?

Answer 22

Nodal (TGF-beta pathway) and Wnt8 (Wnt pathway) are important in organizing the AP axis. Lefty and DKK inhibits Nodal and Wnt, respectively. Anterior region is ‘protected’ from Wnt/Nodal signaling by higher concentrations of Lefty/DKK.

Question 23

What signaling pathway is important in left-right axis distinction?

Answer 23

Nodal signal on left side inhibits signaling on the right side (because Lefty inhibits at greater distance).

Question 24

What does limb / limb bud derive from?

Answer 24

1) ectoderm = skin
2) paraxial mesoderm = somites = muscles.
3) lateral plate mesoderm = skeleton and tendon
4) neural crest cells = sensory neurons.
5) spinal cord = motor neurons

Question 25

Where do somites come from and what do they form?

Answer 25

paraxial mesoderm, gives rise to somites, which give rise to axial segments, which become axial skeleton, skeletal muscles of trunk/limb, dermis and axial tendons.

Question 26

What are the four subdomains of somites?

Answer 26

dermatome, myotome, sclerotome (forms vertebra), syndetome (axial tendons)

Question 27

What is a hox gene?

Answer 27

Gene with a homeobox DNA sequence, found in a gene cluster.

Question 28

What is a homeobox?

Answer 28

DNA sequence that codes for a homeodomain, a protein sequence that can act as a transcription factor for a set of genes involved in embryonic development.

Question 29

What factors are expressed that distinguish anterior and posterior visceral endoderm.

Answer 29

anterior cells express nodal antagonists Cerberus and Lefty and this area becomes the head. Posterior cells express nodal and crypto and become tail.

Question 30

What are the signals that allow for limb bud formation?

Answer 30

Hox gene signal leads to FGF10 activation in lateral plate mesoderm, causes ectoderm above it to express Wnt3a, FGF8 which signals back to mesoderm to maintain FGF10, positive feedback loop that drives limb bud formation. No FGF10 in knock outs causes no limbs.

Question 31

What are the three signaling centers of the limb?

Answer 31

apical ectodermal ridge (proximal-distal), zone of polarizing activity (a/p) dorsal ectoderm (dorsal-ventral)

Question 32

How does proximal/distal signaling work in the limb?

Answer 32

FGF/Wnt distal signal and retinoic acid proximal signal. proximal signal dominates, but as limb bud grows more distal, proximal signal is far away. small primordial elements then expand as limb grows bigger.

Question 33

Preaxial
 polydacytly
 is
 often
 caused 
by
 ectopic
activation
 of 
what 
signaling
 pathway?

Answer 33

SHH

Question 34

What forms the vertebrae?

Answer 34

paraxial mesoderm

Question 35

What is role of FGF and Wnt in somite formation

Answer 35

FGF and Wnt cause growth to extend caudally and inhibits oscillator signals Notch/Delta rostrally to prevent too much boundary formation in the somites.

Question 36

What are the three segments of the limb?

Answer 36

stylopod (proximal element, one bone); Zeugopod (intermediate element, two bones); autopod (wrist, fingers).