Unit 4 - Lecture 21

**Intermediate mesoderm**

Forms the urogenital system (kidneys, gonads, and associated duct systems).

The intermediate mesoderm is specified by which gradient?

BMP gradient.

Higher levels of BMP4 *farther/closer* to the midline.

farther.

For kidney production, besides intermediate mesoderm, another form of mesoderm is necessary. Which one?

A) Chorda mesoderm

B) Paraxial mesoderm

C) Lateral plate mesoderm

B) Paraxial mesoderm

Does cutting paraxial mesoderm away from intermediate mesoderm prevents kidney formation?

Yes. Paraxial mesoderm can even induce lateral plate mesoderm to form some kidney tissues in culture. 

Paraxial mesoderm induces the expression of which three transcription factors?

A) Lim1

B) Fgf2

C) Pax2

D)Nodal

E) Pitx2

F) Pax8

A + C + F) **Lim1**, **Pax2** and **Pax8**.

Kidneys formwhere Lim1 and Pax8 are both expressed. Would expression of Lim1 and Pax8 together in another tissue lead to kidney formation?

Yes.

Mouse Pax2 Pax8 double mutants can still form kidneys (T/F).

False. Can not for kidneys.

Expression of Pax2 in presomiticmesoderm converts it into intermediate mesoderm and causes kidney formation (T/F).

True.

•During embryogenesis, the lateral plate mesoderm splits horizontally into which two layers?

* **Somatic** (**parietal**) **mesoderm**
* **Splanchnic** (**visceral**) **mesoderm**

The somatic mesoderm is formed at the *ventral/dorsal* layer, the splanchnic mesoderm is formed at the *ventral/dorsal* layer.

Ventral, Dorsal.

Somatic mesoderm → ventral

Splanchnic mesoderm → dorsal

**Somatic** (**parietal**) **mesoderm**

Underlies the ectoderm. Together with the ectoderm it forms the **somatopleure**.

**Splanchnic** (**visceral**) **mesoderm**

overlies the endoderm and together with the endoderm forms the **splanchnopleure**. 

**Coelom**

Body cavity, created from the space between the somatopleure and the splanchnopleure. It stretches from the future neck region to the posterior of the body. 

Later in development the left and right sides of the coelom fuse, and folds from the somatic mesoderm divide the coelom into which three separate cavities?

* **Pleural** (envelopment the thorax).
* **Pericardial** (heart).
* **Peritoneal** (abdomen). 

The creation of the body cavity has changed a lot over vertebrate evolution (T/F).

False. It has changed very little, despite difference in gastrulation.

The heart is the first functional organ formed in the embryo (T/F).

True, and the circulatory system is the first functional unit. 

From which mesoderm does the heart arise on both sides of the body?

A) Sclerotome mesoderm

B) Somatic mesoderm

C) Dermatome mesoderm

D) Splanchnic mesoderm

D) **Splanchnic** **mesoderm**

What is the heart precursor cells?

**Carfiogenic mesoderm** (**Heart field**)

Specification of cardiogenic mesoderm begins as these cells migrate inward through the primitive streak during gastrulation. What do they form first?

**Heart tube**

Heart tube

Linear, primitive heart.

What does the **first heart field** form?

The scaffold of the developing heart. It is limited in its proliferative ability and generates only the major portion of the left ventricle of the adult heart (the chamber that pumps blood into the aorta). 

What does the **second heart field** form?

The atria, the base of the aorta, pulmonary arteries, right ventricle, and inflow region (pulmonary veins and vena cava). It also helps form facial muscles and lung mesenchyme.

Nearly all the cells and tissues of the heart derive from the heart fields, including which five?

* **Cardiomyocytes**
* **Endocardium**
* **Endocardial cushions**
* **Epicardium**
* **Purkinje fibers**

**Cardiomyocytes**

Form the muscular layers of the heart.

**Endocardium**

Internal layer of the heart, similar to endothelial cells of blood vessels.

**Epicardium**

Forms the coronary blood vessels that feed the heart.

**Purkinje fibers**

Modified myocytes that control the heartbeat.

Neural crest contribute to the septum. What is the role of the septum?

Separating the aorta from the pulmonary artery, and portions of the outflow tract.

Heart formation is induced by:

A) Anterior ectoderm

B) Posterior ectoderm

C) Posterior endoderm

D) Anterior endoderm

D) Anterior endoderm

What happens to heart formation if anterior endoderm is removed?

No heart

When combining anterior endoderm with mesoderm, does it still form a heart?

Yes.

Which two signals from anterior endoderm induce the heart?

A) BMP2

B) Fgf8

C) Wnts

D) Nodal

E) Pitx2

A + B) **BMP2** and **Fgf8**

Heart tissue is prevented from forming in regions where it shouldn’t by which three factors?

A) Noggin

B) Chordin

C) Wnts

D) Nodal

E) Pitx2

A + B + C) **Noggin**, **Chordin** and **Wnts**

Name two BMP inhibitors.

Noggin and Chordin

What does Wnt alone promote?

Blood and vessel formation.

BMP and other signals activate two key transcription factors for specifying heart field cells.

A) NKx2-5

B) Pitx2

C) Mesp1

D) Fibronectin

E) Fgf2

A + C) **NKx2-5** and **Mesp1**

When are Mesp1 and NKx2-5 first turned on?

When cells migrate through the primitive streak.

**Tinman**

Drosophila NKx2-5 homolog. Acts in heart development.

**Fibronectin**

Responsible for migration of heart field cells. 

Higher concentration of fibronectin in the *anterior/posterior* promote migration.

Anterior

Each side of the lateral plate has heart fields. How are they brought together?

By inward folding of the splanchnopleure to form the foregut.  

**Cardia bifida**

Two separate heart formations. Results from prevention of the merger of the two sides of lateral plate mesoderm.

**Miles apart**

Mutation in zebrafish that results in cardia bifida.

Foregut formation is tied to heart formation (T/F).

True.

1\. Early heart induction is mostly via _____________ and ____________from anterior endoderm.  

A) BMP2; Fgf8 

B) Hairy1; Mesp  

C) Tbx6; Fgf8  

D) Notch; BMP4  

E) Tbx6; Eph  

A) BMP2; Fgf8 

The anterior-posterior specification of different heart regions depends on what?

Retinoic acid-induced Hox gene expression.

RA levels are *highest/lowest* in the posterior in this region at this time, specifying the inflow tracks and atria, which will later loop to the anterior.

highest

RA originated from outside the body can cause heart birth defects (T/F).

True.

Cardiac field cells

A subset of an earlier progenitor population that also gives rise to the circulatory system.

Early progenitor cells give rise to which two structures?

* **Hemangioblasts**
* **Multipotent cardiac precursor cells**

Hemangioblasts give rise to which two structures?

* Hematopoietic (blood) cells.
* Angioblasts (blood vessel cells).

The cardiac fields contain multipotentprogenitor cells that give rise to all the all the different cells of the heart (T/F).

True.

The early mammalian heart is a two- chambered tube, with the inflow (venous) portions in the *anterior/posterior*. 

posterior.

Looping of the heart brings the atrial (inflow) regions to the anterior to make the four chambered heart. Direction of looping depends on which two factors?

A) Pitx2

B) NKx2-5

C) Nodal

D) Fibronectin

E) Wnt

A + C) **Pitx2** and **Nodal**

Mammalian embryos get nutrients from the placenta or the yolk?

Yolk.

Do mammalian embryos utilize the same or different embryonic circulatory system compared to birds and reptiles?

Different.

The right **vitelline vein** of chicks is modified to become what in mammals?

Umbilical vein.

The **allantoic artery**, which carries waste to the allantois in chicks, is modified to become what in mammals?

Umbilical artery.

Mammalian fetal hemoglobin is different than that of adults, and have a slightly *lower/higher* affinity to oxygen, attracting oxygen from the blood of the mother. 

higher

Blood vessels form *dependently/independently* of the heart.

Independently, and link up to the heart soon afterward.

**Vasculogenesis**

A network of blood vessels is created new from the lateral plate mesoderm. 

**Angiogenesis**

The vasculogenesis network is remodeled into a distinct capillary bed, arteries, and veins. 

**Extraembryonic vasculogenesis** (first step)

**Blood islands** form in the yolk sac mesodermal mesenchyme.

**Blood islands**

Made up of **hemangioblasts**, the precursors to both blood cells and blood vessels. 

**Angioblasts**

The cells that form blood vessels.

**Intraembryonic vasculogenesis** (second step)

Forms the dorsal aorta, and this connects with capillary networks that form from mesodermal cells within each organ.

Angioblasts multiply and differentiate into which cells?

**Endothelial** cells.

**Endothelial cells**

From the lining of the blood vessels. These cells form tubes and connect to form a network of capillaries. 

Which two factors are required for vasculogenesis?

A) VEGFs

B) Fgf2

C) Prox1

D) Nodal

E) Pitx2

A) **Vascular endothelial growth factors** (**VEGFs**)

B) **Basic fibroblast growth factor** (**Fgf2**)

Angiogenesis requires which type of VEGF?

VEGF-A

Green tea contains a compound that inhibits VEGF, inhibiting angiogenesis, which may lead to tumor growth suppression and lower incidence of cancer (T/F).

True.

**Lymphatic vasculature**

Forms a separate circulatory system, important for draining fluid and transporting lymphocytes.

During lymphatic vasculature, sprouting from jugular vein in the neck forms what?

Lymphatic sacs.

During lymphatic vasculature, sprouting from the lymphatic sacks forms what?

Peripheral lymphatic.

Which factor specifies lymphatic lineage (and represses blood vessel lineage)?

A) VEGF-C

B) Fgf2

C) Prox1

D) Nodal

E) Pitx2

C) **Prox1**

Which factors promotes lymphatic vessel growth?

A) VEGF-C

B) Fgf2

C) Prox1

D) Nodal

E) Pitx2

A) **VEGF-C**

2\. In the early heart field, Retinoic Acid (RA) levels are highest in the _____________, which specifies the sinus venosus (inflow tracks) and atria.  

A) Anterior 

B) Posterior 

C) Dorsal 

D) Ventral 

E) Ventral midline 

B) Posterior 

Limb development

→

Tetrapod limbs share a common pattern (T/F).

True. Similarities in bone numbers and positions of arms, legs, wings, flippers, etc.

**Stylopod** (**humerus/femur** in arm/leg)

Proximal structure of the tetrapod limb (closest to the body wall).

**Zeugopod** (**radius-ulna/tibia-fibula**)

Middle structure.

**Autopod** (**carpels-fingers/tarsals-toes**)

Distal structure farthest from the body.

Positions of bones are conserved and show similar morphologies among species (T/F).

False. Positions of bones are conserved but show vastly different morphologies among species. 

What are the three axes of the limbs?

* **Proximal-distal** axis
* **Anterior-posterior** axis
* **Dorsal-ventral** axis

Proximal-distal axis of the limb

Proximal = closest to the body

Distal = farthest of the body (fingers)

**Anterior-posterior** axis of the of the llimbs

Anterior = thumb and big toe

Posterior = pinkie and little toe

**Dorsal-ventral** axis of the limb

Dorsal = knuckles

Ventral = palm

When does limb development begin?

When mesenchyme cells migrate from the somatic layer of the limb field lateral plate mesoderm and from the somites at the same anterior-posterior level.

During the starts of limb development, mesenchymal cells accumulate under the ectodermal tissue to form a circular bulge, called:

**Limb bud**

Many different cells are capable of forming limbs (T/F).

False. Only certain cells are capable of forming limbs. Removing these cells prevents limb formation, and transplanting these cells results in limb formation at the new location.

Limb field

Represents all the cells in the embryo capable of forming limbs. It is much larger than the area destined to form the limb, but if limb-specified cells are removed, surrounding limb field cells will form the limb.

The early limb bud contains which three functionally distinct domains?

* **Progress zone** (**PZ**)
* **Zone of polarizing activity** (**ZPA**)
* **Apical ectodermal ridge** (**AER**)

Progress zone (PZ)

The highly proliferative mesenchyme that fuels limb bud growth. It determines proximal-distal fate.

Zone of polarizing activity (ZPA)

The most posterior region of the progress zone. It pattens cell fates along the anterior-posterior axis.

Apical ectodermal ridge (AER)

Thickening of the ectoderm at the apex of the developing limb bud. 

Hox genes specify the identity of a limb along the proximal-distal axis. Which two Hox genes specify stylopod?

* Hox9
* Hox10

Which Hox gene specify zeugopod?

* Hox11

Which two Hox genes specify autopod?

* Hox12
* Hox13

A mouse with Hox10 knockouts lack what?

Femur.