Molecular embryology

Question 1

Shh

Answer 1

• A-P
• mediate left-right axis
• limb patterning
• neural tube induction
• somite differentiation
• gut region differentiation
• differentiation of ventral aspects including motor (ventral horn) neurons
• Holoprosencephaly associated with Shh
  
  • primary defect is incomplete cleavage of developing brain into separate hemispheres & ventricles
  • associated with midline facial defects ex. Cyclopia

Question 2

FGF

Answer 2

• Axon growth
• angiogenesis
• mesodermal differentiation
• limb development
• activates other signaling pathways
• FGFR dimerise & auto-phos and signalvs via Ras-Raf-Mek pathway

Question 3

WNT

Answer 3

• D-V
• urogenital differentiation
• midbrain development
• limb patterning
• associated with:
  
  • colorectal cancer
  • endometroid carcinoma
  • ovarian cancer

Question 4

TGF-Beta

Answer 4

• ECM formation
• epithelial branching (lungs, kidneys, salivary glands)

Question 5

Bone morphogenic protein (BMP)

Answer 5

• bone formation
• spinal cord differentiation-dorsal region

Question 6

HOX genes

Answer 6

Positional info

• segmentation genes:
  
  • divide embryo into segments
  • define the number, size and polarity of each segment
• HOX genes:
  
  • code for transcription factors that bind to a particular sequence of genomic DNA called homeobox
  • expressed in specific segments along the AP axis
  • specifiy the fate of each segment
  • specify adult strucutres formed from the segments
  • HOX D13 associated with synpolydactyly

Question 7

Development of limbs

Answer 7

• appear as small projections on ventrolateral body wall [end of 4th wk]
• upper limb buds appear 26th to 27th day opposite to spinal segments C5-T1
• lower limb buds appear 2 d later opposite to L4-S3
• tip of each limb bud a thickening of ectoderm, Apical Ectodermal Ridge (AER), initiates growth & differentiation of bones & muscles
• AER produces FGFs and is responsible for patterning the proximal distal axis & maintaining proliferation

Question 8

Teratogen: Congenital Rubella

Answer 8

• mother contracting rubella especially during 1st trimester
• Sx:
  
  • low birth wt
  • deafness due to nerve damage CN VIII or hair cells
  • PDA
  • cataracts

Question 9

Teratogen: CMV

Answer 9

• Sx:
  
  • microcephaly
  • hydrocephalus
  • microophthalmia
  • hearing loss
  • mental retardation
    *

Question 10

Teratogen: Congenital Toxoplasmosis

Answer 10

• causative agent: T. gondii
• contaminated cat faeces
• fetus can get infected any time during preg, during labour or during delivery
• at birth, most children are asymptomatic risk of missed dx
• Sx:
  
  • Chorioretinitis
  • hydrocephalus
  • intra-cranial calcifications
  • convulsions
  • Rx: antibiotics (good response)
  • antenatal screening: very important; mother can be rx during preg
  • T: Gondii
  • O: ther
  • R: ubella
  • C: MV
  • H: erpes

Question 11

Teratogen: Congenital Syphyllis

Answer 11

• Treponema pallidum
• STD
• transmission from mother to fetus can occur any time during pregnancy
• very high rate of miscarriages, still births and a multitude of birth defects
• incidence is rising due to increased association with HIV infection
• children infected during labour and delivery have a higher chance of survival as compared to children infected during pregnancy

Question 12

Teratogen: Congenital Varicella

Answer 12

• Infection during 1st & 2nd trimester may rarely cause congenital varicella sx
• Sx:
  
  • cutaneous vesicles & scars
  • limb shortening/malformation
  • neuro anomalies
  • ocular defects
• Rx: pregnancy termination option