Development of Limbs Flashcards
Describe what is created from the lateral plate mesoderm
Splanchic = circulatory system
Somatic = body cavity, pelvis, limb bones and tendons
Extraembryonic
Describe what is created from the intermediate mesoderm
Kidney and gonads
Describe what is created from the paraxial mesoderm
Head and somites
Somites = sclerotome, myotome, dermatome
When do upper limb buds form?
Day 24
When do lower limb buds form?
Day 25-26
What do limb buds form deep to?
The apical ectodermal ridge (AER) which is a thick band of ectoderm that the limb buds form deep to
What grows out from that AER?
Proliferation of mesenchyme from the lateral plate mesoderm
What is the stylopod region?
Humerus or femur
What is the zeugopod region?
Radius/ulna or tibia/fibula
What is the autopod region?
Carpals, metacarpals, phalanges or tarsals, metatarsals, phalanges
What are the axes of the limb bud?
Proximal - Dorsal
Cranial - Caudal
Dorsal - Ventral
Describe the initiation of limb bud growth
FGF10 induces the formation of AER and AER secretes FGF8 which positively regulates FGF10 to stimulate more AER
What is the importance of FGF signaling?
It is essential for the INITIATION of limb bud development and for the proximal - distal axis to form
What happens if AER is completely removed?
NO limb formation
What happens if AER is removed later in development?
Loss of distal elements
Meromelia
Absence of part of a limb caused by intermediate or late loss of FGF signaling
Amelia
Absence of an entire limb caused by early loss of FGF signaling
Phocomelia
Loss of long bones with hands/feet attached proximally
What can cause phocomelia?
Partial loss of FGF signaling or HOX disruption due to thalomide
Adactyly
Absence of digits caused by late loss of FGF signaling
Ectrodactyly
Split hand/foot - “lobster claw”
What causes ectrodactyly
Partial absence of FGF8 from AER or EEC syndrome
What creates the cranial - caudal axis?
Zone of polarizing activity (ZPA)
What supports ZPA function?
SHH!
What happens when there is an overexpression of SHH?
A second ZPA is created and duplicated digits emerge
Polydactyly
Dominant trait; presence of supernumary digits where extra digits lack normal growth and musculature
What do HOX genes regulate?
Cranial - caudal and proximal - distal axes
What is a paralog?
Genes related due to descent from a common ancestral DNA sequence
What hox gene specifies stylopod?
HOX9/10
What hox gene specifies zeugopod?
HOX11
What hox gene specifies autopod?
HOX12/13
Brachydactyly
Shortened finger/toe bones due to genetic changes in HOX13 or PTHLH
What creates the dorsal surface?
Wnt7a
What creates the ventral surface?
EN1 (engrailed)
What gives negative feedback to the Wnt7a?
EN1
How are individual digits formed?
Interdigital mesenchyme apoptosis
What stimulates interdigital mesenchyme apoptosis?
Increased BMP = Increased cell death
When do separate digits fully form?
8th week
What is syndactyly?
Fusion of digits due to no digital rays
What are the 2 types of syndactyly?
Cutaneous and osseous
Cutaneous syndactyly
Webbing between digits fails to degenerate; BMP signaling disruption that causes no apoptosis
Osseous syndactyly
Fusion of bones; HOXD13 mutation
Describe how limbs get their muscle mass
Dermamyotome from the paraxial mesoderm migrates to the limb bud and differentiates into myoblasts to form the ventral and dorsal muscle masses
What does the dorsal muscle mass become?
Extensors, ABductors and supinators
What does the ventral muscle mass become?
Flexors, ADDuctors and pronators
What innervates the dorsal muscle mass?
Dorsal branches of VENTRAL rami
What innervates the ventral muscle mass?
Ventral branches of ventral rami
List the pathway for arterial supply to the upper limb
Dorsal intersegmental A.
Primary axial A.
Brachial A. and common interosseous A.
Ulnar A. and Radial A.
List the pathway for arterial supply to the lower limb
Dorsal intersegmental A.
Primary axial A.
Deep A. of the thigh, Anterior tibial A., Posterior tibial A.
Describe the venous supply
Primary axial A, marginal sinus, peripheral vein
Which way does the upper extremity rotate?
Laterally
Which way does the lower extremity rotate?
Medially
Amniotic bands
Adhesions between amnion and fetal structures; prevents growth or pinches off structure
Bilateral talipes equinovarus
Club foot; caused by oligohydramnios - low amniotic fluid volume reduces fetal movements