test 2: lecture 12 respiratory Flashcards
two types of epithelium in the lungs
airway- more complex- goblet, basal, fibroblasts and smooth muscle- Conduct airflow
alveolar- AT2 and AT1 gas exchange
Lung epithelium is derived from ___
the endoderm (definitive endoderm)
Endoderm is surrounded by visceral ___, derived from the lateral plate mesoderm
“splanchnic” mesoderm
What is expressed to cause lungs to bud and divide from forget endoderm
Nkx2.1
how does respiratory diverticulum develop
Nkx2.1 expressed
- Starts as laryngotracheal groove in the ventral pharynx between the fourth pharyngeal arches.
then the tracheo-esophageal ridge
then the respiratory diverticulum
___ becomes the lining of the trachea, the two bronchi, and the alveoli of the lungs.
Laryngotracheal endoderm
Proper trachea / esophogeal separation requires precise levels of the transcription factor___
Sox2
atresia
dead end- errors in Sox2 and Nkx2.1 that lead to premature stop of esophagus
usually can be surgically fixed
tracheoesophageal fistula
error in trachea and esophagus when they are attached to each other
5 stages of branching morphogenesis of lungs
embryonic
pseudo-glandular
canalicular
saccular
alveolar
embryonic branching morphogenesis of lung
1st stage
Appearance of right and left lung buds
pseudoglandular branching morphogenesis of lung
2nd stage
Complete structure of the human airway tree is complete
canalicular branching morphogenesis of lung
3rd stage
3 more rounds of branching to produce future alveolar regions
saccular branching morphogenesis of lung
4th stage
Branching done. Epithelial growth and differentiation continues
alveolar branching morphogenesis of lung
Secondary septation: subdivision of alveoli to increase surface area for gas exchange
Continues for 21 years!
subdivision of alveoli to increase surface area for gas exchange
secondary septation
happens last stage of branching of lungs- up to 21 years in humans
___ to be expressed in the region of the embryonic foregut endoderm that will bud into the lung
•First transcription factor (TTF1 Nkx2.1)
___ are expressed in the ventral anterior mesoderm surrounding the region of the anterior foregut endoderm and induce expression of Nkx2.1
Wnt2 and Wnt2b
no Wnt, no lungs
expression of Wnt leads to expression of ___ in the lungs. expression of ___ inhibits to Sox2 which will inhibit ___
Nkx2.1
BMP4 Nkx2.1
•BMP4 from the mesoderm ___ Sox2 in the anterior foregut endoderm, thus allowing expression of ___
suppresses/inhibits
Nkx2.1
•(in humans, BMP2 and BMP7 seems to be more important than BMP4)
FGF10 and lung branching
Fgf10 is not required for stereotypic branching
Fgf10 is a permissive factor
not really fully understood
cells that will differentiate into airway cells of the lungs will
turn down Sox2
express Nkx2.1
then turn Sox2 back on
cells that will differentiate into alveolar cells of the lung will
turn down Sox2
express Nkx2.1
then turn on Sox9 and Id2
distal endoderm progenitor lineage
progenitor cells in the developing lung will turn into
proximal progenitors: Sox2
goblet cells, basal cells, ciliated cells ect
distal progenitors: Sox 9, Id2
AEC 1 or 2 (alveolar type 1 (secretory) or type 2 (gas exchange))
goblet cell in the developing lung develop early or late in development?
late
Mechanical forces generated from the inhalation of ___ by ___ movements are essential for AT1 cell differentiation
alveolar cells that move down into the underlying connective tissue by fetal breathing is a ___
alveolar type 2 cell
differences in mouse and human lung development
human alveolar tissue express Sox 2 and Sox 9 until canalicular stage when they express only Sox9
Humans need retinoic acid to differentiate
Mice need ROCK inhibitor to differentiate
the lung professor research does :
Transplantation of human iPSC-derived alveolar type 2 cells into immunocompromised mice
The presence of both the pulmonary arteries and the pulmonary veins in the absence of lung development suggests that ___ contribute to the generation of these structures.
cardiac progenitors
The cardiac progenitors closest to the anterior foregut where the lung arises are defined by expression of ___ and are referred to as the ___
Isl1
second heart field (SHF)
The cardiac progenitors (CPP) cells do not generate ___
alveolar capillaries - still don’t know where these come from
aerocyte
cells that sit on alveolar type 1 cells that help with gas exchange into blood
found in alveoli of lungs
Bronchopulmonary Dysplasia
chronic pediatric lung disease, characterized by impaired gas exchange and respiratory distress
lack surfactant
premature babies are placed on ventilator and oxygen therapy to help breathe but can result in making this disease worse by decreasing alveolar development
you can mimic the effects of Bronchopulmonary Dysplasia by ___ which shows ___
exposing mice to hyperoxia (too much oxygen leads to simplified alveoli)
loss of alveoli type 1 cells- cells revert into type 2 cells in presence of too much O2
pulmonary fibrosis
issue with Alveolar type 2 cells
issue with surfactant production (SFTPC)
Alveolar Type 2 Cell Maturation Promotes __
Parturition (labor)
•Lung maturation is the primary determinant of the ___
timing of labor
•Steroid receptor coactivators 1 and 2, ____, drive expression of Surfactant Protein A and Platelet Activating Factor (an inflammatory phospholipid)
SRC-1 and SRC-2,
