L24 Developmental Genetics

Question 1

Define Totipotent cell, Plasticity and Determination

Answer 1

Totipotent cell: Cell that has the potential to develop into any cell types

Plasticity: The ability of a cell to change its fate depending upon its environment or the genes that it expresses

Determination: A cell becomes committed to a particular cell fate

Question 2

Describe the process of pattern formation?

Answer 2

Pattern Formation:

• The process where ordered spatial arrangements of differentiated cells create tissues and organs
• Caused through semiautonomous regions of the embryo

This usually occurs via several steps:

1. Definition of cells of a region
2. Establishment of signaling centers that provide positional information
3. Differentiation of cells within a region in response to additional cues
   * During pattern formation, the pathways which are activated are integrated to control specific cell fates

Question 3

What are the different developmental stages for fruit flies and the genes that control each of the stage?

How do these genes work in pattern formation?

Answer 3

• Many of these genes work by establishing concentration gradients of morphogens within the developing embryo
• A morphogen is a protein that varies its concentration and elicits different developmental responses at different concentrations
• Many of these morphogens act as transcription factors to activate multiple genes involved with development

Question 4

What are homeotic genes and what does their expression specify?

Answer 4

Homeotic genes:

• Genes play a role in controlling the expression of genes that determine the identity of individual body segments
• The molecular mechanism that is utilized to accomplish this is by acting as DNA-binding proteins
  
  • Region in the homeobox proteins that binds to the DNA is a 60 AA domain that has a protein structure similar to a helix-turn-helix motif

Question 5

What are paracrine factors?

Answer 5

Paracrine factors:

• Proteins that diffuse short distances surrounding a cell to induce a response, similar to those elicited by hormones
• There are 4 main families of paracrine signaling molecules: FGFs, hedgehog, Wnt, & TGF-b
  
  • These bind to cell surface receptors which triggers this response
• Mutations in genes encoding these molecules can lead to abnormal communication between cells

Question 6

What paracrine factor receptor, when mutated, causes Achondroplasia?

Why does this occur?

Answer 6

Achondroplasia (ACH):

• Caused by: Gain-of-Function mutation (Substitution Gly#Arg) in the transmembrane domain of the FGFR3 gene (FGF3 receptor)
  
  • Results in a constitutive activation

FGFR3:

• Normally expressed in non-proliferating chondrocytes where it prohibits chondrocyte proliferation and differentiation
• When activated, the chondrocytes cannot proliferate
  
  • Constituitive Activation leads to short bones & the disproportionate short stature of the individual