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
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
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
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
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
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
What molecules form a gradient for development in the proximal-distal axis?
Retinoic acid -- high proximally
Fgf, Wnt -- high distally
What is the role of the Mesenchyme?
Induce the AER (Fgf-10)
Sustains AER (Fgf-10)
Determines limb type UL or LL
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
What is the fate of the Mesenchyme adjacent to teh AER?
Forms segment specific skeletal elements
Forms fibrous CT
What happens if the AER is removed during developement of a limb?
Limb is truncated
What would cause an amputation along the P-D axis?
Problem with the AER and underlying mesoderm communicating with each other
What is micromelia? Amelia?
Micromelia: Partial limb devo
Amelia: No limb devo
In what axis do the digits develop?
What does the zone of polarizing activity (ZPA) influence?
Patterning along the anterior-posterior axis of the limb
What is a main mediatior in A-P patterning?
Sonic Hedgehog (Shh)
Retinoic acid has the same effect
How does apoptosis play a role in limb development?
Separation of digits
Absence of distal phalanx of large digit
What develops along the dorsal -- ventral axis?
Skeletal muscles: myoblasts organize into dorsal and ventral premuscle masses
Neural and vascular structures
What are some of the main mediators of dorsal-ventral patterning?
What is oligodacytly?
Lobster claw deformity
Causes by longitudinal type absence of limb part along the anterior-posterior axis
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
What is Syndactyly?
Complete or partial fusion of one or more digits
May be due to failure of interdigital apoptosis
What is sirenomelia?
Fused limb fields or abnormal development of tailbud
What is developmental dysplasia of the hip?
A condition where the hip joint is easily dislocated, usually after birth
What is Cleidocranial dysplasia?
Hypoplasia or aplasia of the clavicles
Autosomal dominant inheritance
What is the Sprengel Deformity?
Characterized by a scapula that is located at C4-T2 and are dysplastic