Day 13, Lecture 3 (Sept. 8): Human Development 3: Week 3 in Human Development

Question 1

Question 2

Epithelial vs. Mesenchymal cells

Answer 2

• Epithelial Cells
  
  • Polarized
  • Apical and Basal Surface
  • Sit on top of Extracellular Matrix (ECM)
  • examples
    
    • epidermis
    • intestinal cells
• Mesenchymal Cells
  
  • Not polarized in ECM
  • Surrounded by ECM
  • Migrate through ECM
  • examples
    
    • fibroblast
    • connective tissues
• Epithelial-Mesenchymal Transformation
  
  • During development epithelial cells can transform into mesenchymal cells and mesenchymal cells can transform into epithelial cells

Question 3

in embryo the cranial-caudal axis and anterior-posterior axis is the same

Question 4

Grastrulation

Answer 4

• beginning of the 3rd week of development
  
  • days 15-16
• Process by which the bilaminar embryo becomes trilaminar and the three germ layers are formed:
  
  • Ectoderm
    
    • Outer layer, skin, nervous system
  • Mesoderm
    
    • Middle layer, muscle, heart, skeleton
  • Endoderm
    
    • Inner layer, lining of GI tract
• (note all three germ layers are formed form epiblast)
• Steps of Gastrulation
  
  1. occurs through primitive streak
  2. Primitive streak is formed by thickening of epiblast
  3. Ingression of epiblast through primitive groove forms mesoderm
  4. Epiblast that ingresses through primitive groove replaces hypoblast to form endoderm
  5. Begins early in the 3^rd week of development and is completed by the end of the 4^th week

Question 5

Formation of the Primitive Streak

Answer 5

• Early in the 3rd week of development
• Thickened midline band of epiblast in caudal part of bilaminar disk
• epithelial-mesenchymal transformation
  
  • Requires dramatic change in cell
    
    • loss of cell polarity
    • Change in cell surface receptors
    • reorganization of cell surface receptors
    • Change in cytoskeletal components
  • Factors identified that promote transformation
  • Switch in “master” gene
• ingression of cells between the epiblast and hypoblast
• Primitive groove, primitive knot or node (Hensen’s node), primitive pit
• Migration of mesoderm along midline to form notochord
• Migration of mesoderm laterally to reach extraembryonic mesoderm
• Migration of mesoderm cranially to form cardiogenic region

Question 6

Question 7

Notochord formation

Answer 7

• Mesenchymal-epithelial transformation to form notochordal process
• Forms midline axis- median plane
• Vertebral column forms around notochord
• Notochord degenerates except for between vertebrae were it forms the nucleus pulposus
• Primitive streak regression
  
  • as the notochord progresses the primitive streak regresses caudally
  • Failure of primitive streak to regress leads to Sacrococcygeal Teratoma

Question 8

Answer 8

Question 9

• Neurulation

Answer 9

• process by which the neural tube (future brain and spinal cord) is formed
• Process:
  
  • Notocord (day 18) induces a thickening overlying ectoderm (neuroectoderm) to form neural plate
  • Elevation of the lateral edges of the neural plate form the neural folds and neural groove
  • Closure of neural tube (neuropore) at end of forth week (day 25-27)
  • neural tube forms in the crainal to caudal sequence
• Neural crest cells form as neural tube closes
  
  • form peripheral ganglia (both sensory and autonomic) and Schwann cells of the nervous system

Question 10

How is Neurulation an Example of a Morphogenic Process

Answer 10

• Cells elongate (thicken)
  
  • microtubules responsible
• Apical surface contracts
  
  • actin microfilaments responsible
• Cells become wedge shape
• Change in cell shape leads to tube formation

Question 11

Neural crest cells

Answer 11

• Form from the neuroectoderm
• Neural creast cells referred to as ectomesenchyme
• Form as neural tube closes
• Form:
  
  • peripheral ganglia (both sensory and autonomic) and Schwann cells of the nervous system
  • Dorsal root of spinal cord
  • Pigment cells
  • Brachial arche mesenchyme
• Neural crest cells migrate along defined pathways to reach final destination
• Defects in migration cause
  
  • Hirschsprung’s disease
  • DiGeorge Syndrome
    
    • 3^rd and 4^th brachial arches

Question 12

Neural Tube Defects are detected by

Answer 12

• Ultrasound
• Measuring alpha-fetoprotein (AFP) in amniotic fluid (increased with neural tube defects)

Question 13

Neural tube defects are reduced by

Answer 13

• Folic acid
  
  • Note: it is important to take before pregancy because often women don’t know they are pregant till after the critical period and by then it is too late
• Dietary supplement added to cereal grains

Question 14

Incidence of Neural tube defects

Answer 14

• 1:1000 births (this does not include spinal bifida occulta)

Question 15

Spina Bifida Occulta

Answer 15

• neural tube defect usually with no neural deficit
• failure of the vertebral arches to form
  
  • Small tuft of hair may be seen on lower back

Question 16

Meningocele

Answer 16

• Protrusion of meninges

Question 17

Meningomyelocele

Answer 17

Protrusion of Meninges and spinal tissue

Question 18

Myeloschischisis

Answer 18

No epidermis covering the spinal cord

Question 19

anocephaly

Answer 19

Failure of the anterior neurospore to close

Question 20

Question 21

Anterior-posterior Axis formation

Answer 21

• Anterior visceral endoderm
  
  • essential for development of the cranial part of the embryo
  • secretes cerberus and lefty
    
    • blocks nodal signaling (member of TGF-beta superfamily)
• Caudal formation
• Epiblast throught disk secretes nodal
  
  • signaling blocked anterior by AVE secreting Cerberus and lefty
  • signaling occurs posterior
  • nodal signaling promotes formation of Hensen’s node and primative streak
• Later is Anterior-posterior axis is stabilized by hox genes

Question 22

Primary Body Axis

Answer 22

• Primary body axis is the notocord, neural tube, and somites
• Hensen’s node at cranial end of primitive streak is “organizer” for primary body axis
  
  • Transplantation of Hensen’s node (primitive knot) induces secondary body axis to form
  • (note induction is the process whereby one group of cells determines the development of another group of cells)

Question 23

Molecular Basis for Induction of Primary Body Axis

Answer 23

• Bone morphogenetic protein-4 (BMP-4) expressed throughout embryonic disk
  
  • promotes formation of ventral structures
• Hensen’s node secretes factors that block BMP-4 signaling (Chordin, Noggin, and Follistatin)
• Epiblast cells that ingress through Hensen’s node induced to express Chordin and noggin
  
  • notochord and somites express chordin and noggin
• Due to lack of BMP-4 signaling ectoderm forms notochord, somites, and neuroectoderm

Question 24

Left-Right body axis formation

Answer 24

• Laterality Sequence
  
  • malformation where left-right orientation of organ is abnormal
• Left side determination
  
  • ciliated cells in ventral node of primative node
  • cilia are oriented on cells so that when they beat tey set up right to left flow
  • Nodal vesicular parcels contain sonic hedgehog and retinoic acid
  • promote inhanced expression of secreted factors on left side of primitive streak including nodal and lefty-2
  • induced upregulation of transcription factor PITX2 that estabilishes left-sideness
• Right side-
  
  • not yet determined