Embryo Topic 5

Question 1

Formation of oropharyngeal membrane and cloacal membrane by gastrulation

Answer 1

Longitudinal folding at both ends of the embryo and lateral folding at the sides of the embryo bring the endoderm inside and form the gut tube. Folding creates the anterior and posterior intestinal portals. The cardiac region is brought to the ventral side of the developing gut tube.

Question 2

Oropharyngeal membrane

Answer 2

future mouth

Question 3

Cloacal membrane

Answer 3

future anus

Question 4

Foregut overview

Answer 4

Gut tube proper: pharynx, esophagus, stomach, proximal duodenum
Derivatives of gut tube: thyroid, parathyroid glands, tympanic cavity, trachea, bronchi, lungs, liver, gallbladder, pancreas

Question 5

Midgut overview

Answer 5

Gut tube proper: proximal duodenum to right half of transverse colon

Question 6

Hindgut overview

Answer 6

Gut tube proper: left half of transverse colon to anus
Derivatives of gut tube: urinary bladder

Question 7

What are arteries supply the foregut, midgut, and hindgut?

Answer 7

Foregut: celiac artery
Midgut: superior mesenteric artery
Hindgut: inferior mesenteric artery

Question 8

Regional gut tube patterning and organogenesis

Answer 8

Regional gut tube patterning and organogenesis require bi-directional endoderm-mesoderm cross-talk and inductive signals from other nearby structures. The Hox gene is an example. Hox gene expression is important for formation of major sphincters

Question 9

How is the patterning established?

Answer 9

The Hox gene are evolutionarily conserved transcription factors that are used in regional patterning. The gut has a cranial-caudal Hox gene expression pattern similar to the one in neural tissue. Hox gene expression boundries correspond to morphologically recognizable elements in the GI tract.

Question 10

How does it play out in regional organogenesis?

Answer 10

From the induction of mesodermal Hoxd-13 by Shh the there is regional varieation in competance. Meaning the different regions have varying abilities to respond to certain signals during development. From the restriction of BMP from the stomach mesoderm there is temporal variation in signaling. Meaning that the cells/tissues have the ability to respond to signaling molecule changes over time.

Question 11

Separation of esophagus and trachea

Answer 11

1. Region of foregut just caudal to lung bud develops into esophagus.
2. Endodermal lining is stratified columnar and proliferates such that the lumen is obliterated; opening of lumen is established by canalization.
3. Tube is initially short and must grow in length to “keep up” with descent of the heart and lungs.

Question 12

Fistula

Answer 12

Errors in forming the esophagotracheal septa and/or re-canalization lead to tracheoesophageal fistulas and/or esophageal atresia.
Fistula: abnormal connection

Question 13

Atresia

Answer 13

If recanalization is not done properly than atresia occurs.
Atresia: fully blocked

Question 14

Stenosis

Answer 14

Errors in step 2 cause stenosis. Errors in this process lead to esophageal stenosis. The process of recanalization occurs throughout the gut tube, so this blockage can happen anywhere along the GI tract.
Stenosis: partly blocked

Question 15

Stomach organogensis

Answer 15

Stomach appears first as a fusiform dilation of the foregut endoderm which undergoes a 90° rotation such that the left side moves dorsally. Differential growth occurs to establish the greater and lesser curvatures.

Question 16

Fusiform dilation

Answer 16

Fusiform dilation is the gradual, uniform widening of a vessel, typically an artery, in a spindle-shaped fashion.

Question 17

Differential growth

Answer 17

Refers to the unequal or varying growth rates of different parts of an organism or tissue during development.

Question 18

Signals for liver formation

Answer 18

FGFs secreted by cardiac mesoderm and BMPs secreted by septum transversum induce liver and foregut endoderm. Endothelial cells supply critical growth signals which are:
- FGF from cardiac mesenchyme
- BMPs from septum transversm mesenchyme
- VEGF from endothelial cells

Question 19

Pancreas formation/signaling

Answer 19

Signaling from the notochord represses Shh in foregut endoderm, which permits pancreatic differentiation.

Question 20

Midgut and colon formation

Answer 20

While herniated, gut undergoes a primary rotation of 90º “counterclockwise” (when
looking at the embryo); this corresponds with the rotation of the stomach, and positions the appendix on the left.
With the growth of the embryo, the
abdominal cavity expands thus drawing the gut tube back within the abdominal cavity and causing an additional, secondary rotation of 180º CCW (positioning the appendix on the RIGHT)

Question 21

Respiratory tract development: mesoderm dependent process

Answer 21

Retinoic acid produced by adjacent
mesoderm induces expression of TBX4 in foregut endoderm. TBX4
induces growth and differentiation of the trachea and lungs.

Question 22

Tracheo-esophageal ridges

Answer 22

Longitudinal ridges that
eventually fuse to separate trachea from esophagus.

Question 23

Differentiation of pleural membranes

Answer 23

The lung buds “punch” into the visceral mesoderm. The mesoderm, which covers the outside of the lung, develops into the visceral pleura. The somatic mesoderm, covering the body wall from the inside, becomes the parietal pleura. The space between is the pleural cavity.

Question 24

Separation of abdominal and thoracic cavities

Answer 24

• The septum transversum begins to form and partially divides the abdominal and thoracic cavities.
• It grows from front to back in a roughly horizontal plane.
• Initially at the level of C1, it moves downward due to differential growth of the embryo.
• Between weeks 5-6, myoblasts move into the septum, bringing the phrenic nerve with them (originating from C3, C4, and C5).
• By week 8, the septum angles downward so the front is near T7 and the back is near T12, similar to its position in adults.
• The septum stops at the gut tube, leaving two open passageways on the left and right called the pericardioperitoneal canals
• The closing of these canals requires growth from the dorsolateral body wall, forming the pleuroperitoneal membranes.

Question 25

Initial patterning of the lung

Answer 25

First three branching events are stereotyped: - Trachea into two primary bronchi (left and right) - Left primary bronchus into two secondary bronchi (corresponding to the two lobes of the left lung) - Three secondary buds form on the right (corresponding to the 3 lobes on the right) - Ten tertiary (segmental) bronchi form in the right lung and - Eight bronchi form in the left lung - establishing the 18 brochopulmonary segments of the adult human lung.

Question 26

Signals for lung budding and branching

Answer 26

- Tbx/RA signaling activates the mesenchyme to release FGF10, which promotes epithelial growth. - BMP4 is secreted by apical epithelial cells, triggering branching and halting their proliferation. - The epithelium also secretes Shh, which inhibits mesenchyme proliferation and FGF10 secretion. - Mesenchymal cells release TGFβ, which encourages ECM deposition. - FGF10 signaling continues at the lateral aspects of the lung, promoting growth on both sides. Branching morphogenesis in the lungs is mesoderm and retinoid-dependent. Late disruption may have minor effects whereas early disruption may result in hypoplasia or even agenesis.