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Flashcards in Limb Development Deck (27)
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1

What are the limb fields? 

Areas of somatic mesoderm on each side of the embryo at specific axial levels 

Axial positioning is regulated by Hox genes 

Tbx5 transcription factor for upper limbs 

Tbx4 and Pitx-1 transcription factor for lower limbs

2

What is budding and when does it occur? 

During week 4: UL 26-27d, LL 28-29d

Small elevations on each side of the embryo at specific axial levels

Formed d/t inherent property of somatic mesoderm, begins producing Fgf-10

3

What does Fgf-10 induce?

Release of Fgf-10 by mesenchyme cells causes the surface ectoderm to form a thickened ridge of ectoderm -- Apical Ectodermal Ridge (AER): runs anterior to posterior along the interface between the dorsal and ventral surfaces of the limb bud 

4

What occurs during elongation of the limb? 

Limb buds change shape 

Week 5: flat paddle shaped hand/foot at distal end

Week 6: three segments are visible and digital rays are visible in hand/foot

Week 8: UL digits are complete separate, LL remain partially separated 

Devo of upper limb usually precedes that of lower limb by about 1-2 days

5

When does tissue formation and organization occur? 

Begins during week 5 in proximal limb -- continues in proximal - distal direction

Somatic mesoderm condenses to form cartilage models of limb bones

Somite-derived mesoderm cells migrate to form skeletal muscles 

Motor axons of spinal nerves also enter the limb 

6

What are the three sets of linear axes and what develops along them?

Proximal-distal: limb outgrowth and elongation

Anterior posterior: develops digits

Dorsal-ventral: muscles and neurovascular structures form and are subdivided 

7

8

What molecules form a gradient for development in the proximal-distal axis?

Retinoic acid -- high proximally 

Fgf, Wnt -- high distally 

9

What is the role of the Mesenchyme? 

Induce the AER (Fgf-10) 

Sustains AER (Fgf-10) 

Determines limb type UL or LL 

10

What is the role of the AER? 

Maintain a proliferating pool of mesenchyme cells for linear growth (Fgf-8)

Maintain an A-P axis signaling center - ZPA (zone of proliferating activity) 

Interacts with P-D and A-P specific proteins to provide mesenchyme cells with positional information 

11

What is the fate of the Mesenchyme adjacent to teh AER? 

Forms segment specific skeletal elements

Forms fibrous CT

12

What happens if the AER is removed during developement of a limb?

Limb is truncated 

13

What would cause an amputation along the P-D axis? 

Problem with the AER and underlying mesoderm communicating with each other 

14

What is micromelia? Amelia? 

Micromelia: Partial limb devo

Amelia: No limb devo

15

In what axis do the digits develop? 

Anterior-posterior axis

 

16

What does the zone of polarizing activity (ZPA) influence? 

Patterning along the anterior-posterior axis of the limb

17

What is a main mediatior in A-P patterning? 

Sonic Hedgehog (Shh) 

Retinoic acid has the same effect 

18

How does apoptosis play a role in limb development? 

Separation of digits

Absence of distal phalanx of large digit

19

What develops along the dorsal -- ventral axis? 

Skeletal muscles: myoblasts organize into dorsal and ventral premuscle masses 

Neural and vascular structures

Limb compartmentalization

20

What are some of the main mediators of dorsal-ventral patterning? 

21

What is oligodacytly? 

Lobster claw deformity

Causes by longitudinal type absence of limb part along the anterior-posterior axis 

22

What is Phocomelia? Which drug commonly caused this before being banned? 

Distal segment of limb is attached to a more proximal segment with the intervening segment missing or may be directly attached to the girdle 

23

What is Syndactyly? 

Complete or partial fusion of one or more digits

May be due to failure of interdigital apoptosis 

24

What is sirenomelia? 

Fused limb fields or abnormal development of tailbud 

25

What is developmental dysplasia of the hip?

A condition where the hip joint is easily dislocated, usually after birth 

26

What is Cleidocranial dysplasia? 

Hypoplasia or aplasia of the clavicles 

Usually bilateral 

Autosomal dominant inheritance 

Runx-2 gene

27

What is the Sprengel Deformity? 

Undescended scapula

Characterized by a scapula that is located at C4-T2 and are dysplastic