Embryology of the Lungs

Question 0

What do primary, secondary, and tertiary buds correspond to in the adult lung?

Answer 0

Primary: 2 main bronchi.
Secondary: 2 left lobes, 3 right lobes.
Tertiary: 8(ish) left segments, 10 right segments.

Question 1

What process separates the trachea from the esophagus?

Answer 1

Septation.

Failed sepatation -> tracheo-esophageal fistulae.

Question 2

Terminal bronchioles form… and then terminal sacs form.

Answer 2

Okay… that’s a sensible order for that to happen in.

Question 3

4 periods of lung development? (… the slides start at period II)
What gestational age range does each happen in?
Notable structure?

Answer 3

II: Pseudoglandular Period, 6-16 wks, terminal bronchioles.
III: Canalicular Period, 16-26 wks, 1st terminal sacs (first possibility of gas exchange).
IV: Terminal Sac Period, 26 wks -birth, Type I and II epithileal cells.
V: Alveolar period, 32 wks - 8 years, more alveoli and surfactant.

Question 4

What do Type II epithelial cells do?

Answer 4

Make surfactant.

Serve as stem cells.

Question 5

What does “maturation” of terminal sacs into alveoli entail?

Answer 5

Type I epithelial cells thin to allow better gas exchange.

Question 6

What tells the growing conducting ducts to branch?

Answer 6

The mesenchyme…. it tells the ducts what level they’re at and how much they should branch.

Question 7

What’s a signaling molecule particularly found in distal mesenchyme that tells ducts to act distal-ish?

Answer 7

FGF10.

Question 8

In branching… what grows, and what doesn’t grow?

Answer 8

Tips grow (highly mitotic).
Spaces between tips/buds have growth inhibitors present. (such as Sprouty)

Question 9

What might specifically inducing branching at the tip of a growing bud?

Answer 9

Sonic hedgehog (Shh) inhibits FGF10.

Question 10

How are distal and proximal duct epithelial cell morphologies distinct?

Answer 10

Proximal - ciliated, psuedostratified guys.
Distal: Type I and Type II epithelial cells.
(this involves Wnt, BMP, and Gremlin, but that’s almost too silly to talk about)

Question 11

Okay, but if we really want to talk about Wnt, BMP, and Gremlin, what do they do with regards to lung epithelium morphology?

Answer 11

WNT and BMP induce distal epithelial.
Gremlin inhibits distal epithelial differentiation.

(if you don’t have WNT… you have more ciliated epithelium)

Question 12

Cardiopulmonary progenitors mediate connection between lung and heart.

Answer 12

Good.

Question 13

What causes respiratory distress syndrome RDS?

Answer 13

Insufficient surfactant.

Question 14

What does the other lung do when there’s 1 lung that just doesn’t form at all?

Answer 14

it grows to be bigger.

Question 15

Congenital diaphragmatic hernia. Why it bad for the lungs?

Answer 15

If smooshed, the lungs don’t fully develop.

Question 16

What’s a bronchogenic cyst?

Answer 16

Lung tissue where it’s not supposed to be - budding off some other part of the gut tube.

Question 17

What’s Congenital Cystic Adenomatoid Malformation (CCAM)?

Answer 17

CCAMs are from messed up branching… too many terminal bronchioles with too few alveoli… or something.

A mouse model with too much FGF10 resembles CCAM.

Question 18

Mutation in what non-surfactin protein will cause the same phenotype as mutations in surfactin B and surfactin C.

Answer 18

The ATP-dependent transporter, ABCA3.

(because ABCA3 transports those proteins… in some important step0

Question 19

What disease might result from the reactivation of things like BMP, Wnt, TGFbeta, and Gremlin?

Answer 19

Idiopathic Pulmonary Fibrosis

Question 20

Difference in regeneration in to mild vs. “dramatic” injury to the lung epithelium?

Answer 20

Mild - differentiated cells divide.

Dramatic - basal cells act as stem cells to replace various cell types, and can travel quite far.