Lecture 29 - Limb Development and Malformations

Question 1

____________ give(s) rise to limb CONNECTIVE tissues including the SKELETON and tendons.

Answer 1

Lateral mesoderm cells

Question 2

MUSCLE cells of the limb come from the adjacent ________ and migrate into the limb at early limb bud stages.

Answer 2

somites

Question 3

The _______ is a limb bud signaling center in the region of posterior lateral mesoderm.

Answer 3

zone of polarizing activity (ZPA)

Question 4

The _______ is a signaling center that presents as a thickening at the tip of each bud.

Answer 4

apical ectodermal ridge (AER)

Question 5

The critical period for limb development is: A. 2-4 weeks B. 4-7 weeks C. 4-5 weeks D. 3-6 weeks E. 3-8 weeks

Answer 5

E.

Question 6

“Fused digits” are described as what congenital malformation: A. Syndactyly B. Polydactyly C. Polyamelia D. Brachyamelia E. Septodactyly

Answer 6

A.

Question 7

“Extra digits” as described as what congenital malformation? A. Syndactyly B. Polydactyly C. Polyamelia D. Brachyamelia E. Septodactyly

Answer 7

B.

Question 8

“Clubfoot” describes a range of abnormalities in which the foot is turned:

Answer 8

inward and downward

Question 9

“Missing proximal elements” are described as what congenital malformation:

A. Syndactyly

B. Polydactyly

C. Brachydactyly

D. Brachyamelia

E. Phocoamelia

Answer 9

E.

Question 10

RA and Wnts are produced by somitic mesoderm and lateral plate mesoderm. What do they help regulate?

Answer 10

transcription factors that define forelimb vs. hindlimb identity

Question 11

A major function of Tbx genes is to initiate limb bud outgrowth. Tbx4 and Tbx 5 do so by regulating:

Answer 11

expression of FGFs

Question 12

Which is regulated by Pitx1, which encodes hindlimb identity? A. Tbx1 B. Tbx4 C. Tbx5 D. RA E. Wnts

Answer 12

B.

Question 13

Which Tbx gene operates at forelimb levels and encodes forelimb identity?

Answer 13

Tbx5

Question 14

_______ initially promotes the transition of flank mesoderm from an epithelial to a mesenchymal population.

Answer 14

FGFs

Question 15

Which signaling center of the limb bud is an important source of FGFs?

Answer 15

apical ectodermal ridge (AER)

Question 16

Which is false regarding the outgrowth of the limb? A. the AER is required for limb outgrowth B. the earlier the AER is removed, the more severe the truncation of the limb. C. Addition of FGFs will not compensate for AER removal. D. FGFs appear to promote cell survival and cell proliferation

Answer 16

C. Addition of FGFs to the region of an ablated AER will correct or compensate for AER removal.

Question 17

What is the role of Hox proteins in limb formation?

Answer 17

Hox proteins play a role in the definition of proximodistal (PD) limb regions, and are expressed in ‘nested’ patterns within the developing limb buds.

Question 18

Which protein leads to changes in the expression and function of Gli transcription factors?

Answer 18

Sonic hedgehog

Question 19

Shh signal transduction takes place in association with _______.

Answer 19

primary cilia

Question 20

Shh binds to a receptor complex in the membrane that consists of:

Answer 20

Patched and Smoothened proteins. *Note: binding by Shh alleviates the repression of Smoothened by Patched.

Question 21

Which signaling center of the limb bud is defined by its ability to induce mirror-image duplications of the digits?

Answer 21

The Zone of Polarizing Activity (ZPA)

Question 22

________ signaling promotes mesenchyme proliferation and expansion of the limb.

Answer 22

Shh

Question 23

Inactivation of Shh results in the loss of:

Answer 23

all but digit 1

Question 24

Shh regulates the expression of _____ in most distal limb regions, leading to the establishment of digit identity.

Answer 24

Hox

Question 25

During early AP patterning, how does Shh act on Gli3?

Answer 25

Shh converts Gli3 from repressor to activator of downstream target genes.

Question 26

How do BMPs mediate interdigital cell apoptosis in late stages?

Answer 26

via signaling to the AER to decrease FGF expression

Question 27

Which is responsible for variable upper arm defects? A. Hox genes B. Gli3 C. Pitx1 D. Tbx5

Answer 27

D. Tbx5 is linked to defects such as carpal bone fusion, absent or triphalangeal thumb, syndactyly, etc.

Question 28

Which is responsible for lower limb defects? A. Hox genes B. Gli3 C. Pitx1 D. Tbx5

Answer 28

C. Pitx1 is responsible for defects such as clubfoot and polydactyly.

Question 29

Which is responsible for several abnormalities of the hand and foot? A. Hox genes B. Gli3 C. Pitx1 D. Tbx5

Answer 29

A.

Question 30

Which is NOT primarily responsible for polydactyly? A. Hox genes B. Gli3 C. Pitx1 D. Tbx5

Answer 30

D. Despite several factors being linked to this, the Shh signaling pathway and Gli3 are common causes.

Question 31

Thalidomide disrupts _______ formation.

Answer 31

blood vessel

Question 32

Thalidomide exposure reduces limb levels of \_\_\_\_\_, leading to the death of cells in limb bud mesenchyme and the AER.

Answer 32

FGFs

Question 33

What are the four components of the atrial septum?

Answer 33

1. Septum primum 2. Dorsal mesenchymal protrusion 3. Endocardial cushions 4. Septum secundum

Question 34

A defect in closure of the ostium primum (i.e. septum primum does not fuse with endocardial cushions) results in: \_\_\_\_\_\_. A. Primum ASD B. Secundum ASD C. Common AV Canal D. Common atrium

Answer 34

A. Primum ASD

Question 35

Abnormally large ostium due to excessive resorption of septum primum or insufficient septum secundum is what type of defect? A. Primum ASD B. Secundum ASD C. Common AV Canal D. Common atrium

Answer 35

B.

Question 36

A _________ is a defect that is a large hole in the center of the heart (i.e. an endocardial cushion defect). A. Primum ASD B. Secundum ASD C. Common AV Canal D. Common atrium

Answer 36

C.

Question 37

\_\_\_\_\_\_\_\_ is a complete absence of atrial septa. A. Primum ASD B. Secundum ASD C. Common AV Canal D. Common atrium

Answer 37

D

Question 38

What major part of the heart receives contributions from the neural crest cells? A. AV Canal B. Atrial septa C. Ventricular septa D. Truncal septa

Answer 38

D. Truncal septa, or the outflow tract, arises from the cranial neural crest cells and the SHF cells. These contribute to the truncal cushions and their derivative, the aorticopulmonary septum.

Question 39

A _____________ is a lack of separation of aortic and pulmonary trunks due to failure of cushion formation, defective cushions, or abnormalities in the neural crest cells. A. Transposition of the Great Vessels B. Persistent Truncus arteriosus C. Ventricular septal defect D. Tetralogy of Fallot

Answer 39

B.

Question 40

In one particular defect, the aorta and pulmonary trunks are reversed such that the aorta arises from the right and the pulmonary trunk from the left ventricle. A. Transposition of the Great Vessels B. Persistent Truncus arteriosus C. Ventricular septal defect D. Tetralogy of Fallot

Answer 40

A. This is thought to reflect failure of truncal cushions and septa to spiral, which in turn may reflet abnormal rotation of the atria.

Question 41

\_\_\_\_\_\_\_ is the most common cardiac defect and usually an incomplete interventricular septum. A. Transposition of the Great Vessels B. Persistent Truncus arteriosus C. Ventricular septal defect D. Tetralogy of Fallot

Answer 41

C. VSD is caused by: a) deficient development of conal cushions b) failure of fusion of intramembranous and muscular septa c) failure of AV cushion development and/or fusion d) insufficient development of the muscular septum

Question 42

Which is NOT a primary cause of VSD? A. deficient development of conal cushions B. failure of fusion of intramembranous and muscular septa C. failure of the truncal cushions and septa to spiral D. failure of AV cushion development and/or fusion E. insufficient development of the muscular septum

Answer 42

C. This is a feature of "Transposition of the Great Vessels", not VSD.

Question 44

Problems with Shh signaling at the _________ often result in polydactyly and are linked to Gli3 regions.

Answer 44

Zone of polarizing activity