Embryology Flashcards
When do limb buds appear?
At 4 weeks
3 planes of limb bud development
Proximal-distal, dorsal-ventral, anterior-posterior
What gene regulates proximal-distal limb development
FGF
Describe production of FGF
Initially produced by mesoderm which causes the AER to form, then produced by AER to signal proliferation in mesoderm
Describe how digits form
Apoptosis of cells in the AER to separate it into five digits
Wnt-7a
Signalling protein expressed by AER that activates LMX-1 in the mesoderm to form dorsal structures
LMX-1
Activated by Wnt-7a, responsible for forming dorsal structures
Deletion of LMX-1 causes
both sides to be ventral
Engrailed1
Activated by the ectoderm on the ventral side of the limb to repress WNT-7a, to create a ventral and dorsal side
Shh
Signalling protein produced at posterior base of limb buds
Zone of Polarizing Activity
Area that produces Shh
Placing Shh or ZPA to anterior limb bud would cause
mirror duplication of structures
Hox genes
Activated by Shh diffusing across limb bud, responsible for differentiation pattern of anterior-posterior digits and segmental organization of entire embryo cranial-caudal
Gene responsible for proximal-dorsal limb development
FGF
Genes responsible for dorsal-ventral limb development
Wnt-7a, LMX-1, engrailed1
Genes responsible for anterior-posterior limb development
Shh, Hox
Genes responsible for cranial-caudal segmental organization of embryo
Hox
Ossification type used for long bones
Endochondral ossification
Ossification type used for flat bones of skull and face
Intramembranous ossification
Mesenchyme
Loosely organized, mesodermal tissue that develops into connective and skeletal tissues
Process of intramembranous ossification
Mesenchyme cells differentiate directly into osteoblasts
Process of intramembranous ossification
Mesenchyme differentiates into chondroblasts which produce a cartilage model that then becomes vascularized, introducing osteoblasts. Chondrocytes get stuck at the epiphyses.
Layers of epiphyseal plate
Resting, proliferation, hypertrophy, calcification, ossification
Zone of calcification
where chondroblasts mineralize the surrounding matrix
Zone of hypertrophy
where chondroblasts undergo apoptosis
Zone of ossification
where osteoblasts bind to mineralized matrix and deposit bone matrix
What area of trilaminar embryo becomes skeletal muscle?
Paraxial mesoderm (closest to notochord and neural tube)
Somites
Segments in a cranial-caudal sequence in the trunk
Somites differentiate into
Axial skeleton, some dermis, all skeletal muscle
When do axons of motor neurons enter the limb bud
During 5th week
When do axons of sensory neurons enter the limb bud
Soon after the motor neuron axons enter
Dermatome
Area of the skin innervated by one spinal nerve
When do limbs rotate?
6-8 weeks
In what way do limbs rotate?
Arms laterally and legs medially
When are embryos susceptible to limb malformations?
4-5 weeks
Reduction deficit
All or part of limb is missing
Types of reduction deficit
Meromelia, amelia, phocomelia
Thalidomide effects
Amelia at week 4, meromelia at week 5
Mechanism of thalidomide
Disrupts AER and its production of FGF
Duplication defect
Extra limb elements are present
Example of duplication defect
Polydactyly
Polydactyly
Shh is expressed in anterior limb bud, causing mirror extra digits. Caused by ZPA duplication
Dysplasia
Malformation of part of limb
Example of dysplasia
Syndactyly
Syndactyly
Abnormal fusing of the digits from reduced apoptosis in AER
