W5 Embryology

Question 1

• Embryo folding

Answer 1

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)

Question 2

• Mesoderm parts

Answer 2

o Paraxial mesoderm (either side of neural tube)
o Intermediate mesoderm (next to paraxial)
o Lateral plate

Question 3

• Lateral plate mesoderm

Answer 3

o Divided into somatic mesoderm and splanchnic mesoderm
o Somatic is in contact with ectoderm
o Splanchnic is in contact with endoderm

Question 4

• Splanchnic mesoderm

Answer 4

o Surrounds the gut tube and forms wall of gut

o Also called visceral mesoderm

Question 5

• Somatic mesoderm

Answer 5

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

Question 6

• Paraxial mesoderm

Answer 6

o Forms axial skeleton

o Skeletal muscles in the body wall and limbs

Question 7

• FGF8

Answer 7

o Produced by intermediate mesoderm

o Induces lateral plate mesoderm to produce FGF10

Question 8

• FGF10

Answer 8

o Produced by lateral plate mesoderm

o Induces overlying ectoderm to form apical ectodermal ridge (AER)

Question 9

• AER

Answer 9

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

Question 10

• ZPA

Answer 10

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

Question 11

• Shh

Answer 11

o Sonic hedgehog

o Established gradient of Hox gene expression across developing limbs

Question 12

• Hox genes

Answer 12

o Transcription factors that define pattern of differentiation from thumb to little finger

Question 13

• Polydactyly

Answer 13

o Caused by transplantation of the ZPA or implantation of Shh bead to anterior limb bud

Question 14

• Intramembranous ossification

Answer 14

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)

Question 15

• Endochondral ossification

Answer 15

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

Question 16

• Epiphyseal plate

Answer 16

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

Question 17

• Somitomeres

Answer 17

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

Question 18

• Sclerotome

Answer 18

o Axial skeleton
o Cells of ventral and medial wall of somite lose epithelial arrangement and migrate in direction of notochord and become scelrtome

Question 19

• Dermatome

Answer 19

o White, dermis of skin

Question 20

• myotome

Answer 20

o red, skeletal muscle

o splits into epimere and hypomere

Question 21

• epimere

Answer 21

o develops into intrinsic back muscles

Question 22

• hypomere

Answer 22

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

Question 23

• axons of motor neurons

Answer 23

o enter limb bud during 5th week and grown into dorsal and ventral masses

Question 24

• axons of sensory neurons

Answer 24

o enter limb bud after meteor axons and supply segmental regions of skin (dermatome)

Question 25

• limb defects

Answer 25

o	rare 
o	6/10,000 live births
o	Mainly hereditary
o	4th-5th weeks are most susceptible 
o	Three categories

Question 26

• Reduction defect

Answer 26

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

Question 27

• Duplication defects

Answer 27

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

Question 28

• Dysplasia

Answer 28

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