W5 Embryology Flashcards
• Embryo folding
o Occurs between days 18-24 after fertilization
o Trilaminar embryo undergoes cranial-caudal and lateral folding to form the tube within a tube body plan
o As a result, top of yolk sac becomes gut tube which is suspended within the tube of the body by mesoderm
o Mesoderm becomes the gut tube (wall of gut, connective tissue, smooth muscle, blood vessels)
o Endoderm become epithelium lining of the gut
o Ectoderm and mesoderm are brought around embryo to form anterior body wall and encase the embryo in amniotic cavity
o Ectoderm becomes epithelium of skin
o Mesoderm underlying the ectoderm becomes components of body wall and limbs (bone, connective tissue, smooth muscle, blood vessels)
• Mesoderm parts
o Paraxial mesoderm (either side of neural tube)
o Intermediate mesoderm (next to paraxial)
o Lateral plate
• Lateral plate mesoderm
o Divided into somatic mesoderm and splanchnic mesoderm
o Somatic is in contact with ectoderm
o Splanchnic is in contact with endoderm
• Splanchnic mesoderm
o Surrounds the gut tube and forms wall of gut
o Also called visceral mesoderm
• Somatic mesoderm
o Separated from splanchnic by body cavity
o Forms components of body wall and limbs
o Forms connective tissue and smooth muscle in body wall and libs
o Appendicular skeleton
• Paraxial mesoderm
o Forms axial skeleton
o Skeletal muscles in the body wall and limbs
• FGF8
o Produced by intermediate mesoderm
o Induces lateral plate mesoderm to produce FGF10
• FGF10
o Produced by lateral plate mesoderm
o Induces overlying ectoderm to form apical ectodermal ridge (AER)
• AER
o Thickened ectoderm that maintains proliferation of underlying somatic mesoderm cells (progress zone) through production of FGF4 and FGF8
o Promotes outgrowth of limb bud along proximal/distal axis (shoulder to fingers)
o As limb elongates the cells leave the progress zone and are no longer under influence of AER – cells stop dividing and differentiate into cartilage and bone
o Without AER – distal truncation of limb
o Selective loss of AER – facilitates digit formation by reducing FGF amounts in interdigital space leading to cell apoptosis and cessation of cell proliferation in these areas
• ZPA
o Zone of polarizing activity
o Specialized mass of cells in base of the limb bud that regulates development along cranial/caudal axis
o Induced by FGF8 and AER and helps maintain AER through production of retinoic acid (vitamin A)
o Vitamin A initiates expression of Shh which regulates anteroposterior aspect
• Shh
o Sonic hedgehog
o Established gradient of Hox gene expression across developing limbs
• Hox genes
o Transcription factors that define pattern of differentiation from thumb to little finger
• Polydactyly
o Caused by transplantation of the ZPA or implantation of Shh bead to anterior limb bud
• Intramembranous ossification
o Formation of the flat bones of the skull and bones of the face
o Mesenchyme is loosely organized, mainly mesodermal embryonic tissue that develops into connective and skeletal tissues (including blood and lymph)
o Mesenchyme cells differentiate into osteoblasts and produce primary or woven bone (irregularly arranged collagen fibers)
o Woven bone is remodeled to lamellar bone (alignment of collagen into sheets)
• Endochondral ossification
o Formation of long bones, vertebral column, pelvis, sternum, and skull base
o Mesenchyme differentiates into chondroblasts which produce cartilage model
o Cartilage becomes vascularized and is replaced by bone matrix
o Cartilage remains on the surface of epiphysis as the articular cartilage and in between the epiphysis and diaphysis at the epiphyseal plate which regulates growth in length
• Epiphyseal plate
o Cartilaginous structure responsible for growth in length of long bones
o Proliferation occurs at the epiphyseal side of the plate and replacement by bone occurs at the diaphyseal side
o Bone continues to grow as long as the rate of cell division equals the rate of cell death and ossification
• Somitomeres
o Segments of paraxial mesoderm
o Form in a craniocaudal sequence
o Somitomeres 1-7 contribute mesoderm to head and neck
o Remaining condense into somites
o Somites differentiate into sclerotome, myotome, and dermatome
• Sclerotome
o Axial skeleton
o Cells of ventral and medial wall of somite lose epithelial arrangement and migrate in direction of notochord and become scelrtome
• Dermatome
o White, dermis of skin
• myotome
o red, skeletal muscle
o splits into epimere and hypomere
• epimere
o develops into intrinsic back muscles
• hypomere
o develop into limb and body wall muscles
o dorsal and ventral condensation: migrate to limb bud to become skeletal muscles of the limbs
o dorsal condensation gives rise to extensors
o ventral condensation gives rise to flexors
• axons of motor neurons
o enter limb bud during 5th week and grown into dorsal and ventral masses
• axons of sensory neurons
o enter limb bud after meteor axons and supply segmental regions of skin (dermatome)
• limb defects
o rare o 6/10,000 live births o Mainly hereditary o 4th-5th weeks are most susceptible o Three categories
• Reduction defect
o Part of (meromelia) or entire limb (amelia) is missing
o Phocomelia is a type of reduction when hands or feet project directly from shoulder or hip
o Thalidomide caused meromelia at week 5 and amelia at week 4
o Mechanism of disruption is AER
• Duplication defects
o Polydactyly
o ZPA mechanism
o Shh is ectopically expressed in anterior limb bud as well as usual posterior expression
o Can be inherited or teratogen induced
• Dysplasia
o Malformation of part of limb (syndactyly – abnormal fusion of digits resulting from reduced apoptosis)
o Mechanism is that AER does no break down between digits, so apoptosis does not occur normally when forming digits