Molecular Regulation of Development

Question 1

Describe the transcription factors with respect to structure and method of interaction with DNA.

Answer 1

Structure:
– Proteins with domains that bind to promoter regions &
domains that interacts with RNA polymerase II
– Regulates the amount of mRNA that the gene produces

Question 2

Describe the relationship between homeobox-containing genes and homeodomain proteins

Answer 2

Homeobox containing genes (DNA sequence) codes for–> homeodomain proteins (TF’s)

Homeobox containing genes: HOX genes

Homeodomain proteins: (TF). Has Homeodomain (60 amino acid helix turn helix DNA binding domain) which allows protein to bind directly to DNA as TF, activating other genes and directing formation of embryo

Question 3

Compare and contrast the function of Hox genes, Pax genes, Lim proteins, Dlx genes and Msx genes, the T-Box gene family and basic Helix-Loop-Helix proteins

Answer 3

HOX genes: “head to tail development”, regulated by retinoic acid (Vit A), HOX genes lay out big pattern and retinoic acid makes boundaries

Pax: Early formation of organs, tissues. CNS/sense organs, pancreas, maintaining normal function of certain cells after birth

Lim proteins: Formation of all body segments, absence can lead to headless mammalian embryos, like HOX-big pattern development

Dlx genes: role in outgrowing appendages in early embryogenesis, shaping of jaws and inner ear

Msx genes: -prenatal- inhibitors of cell differentiation

• Post-natal: help tissues to keep dividing
• Involved w/ bones on skull, face and limbs
• Teachers daughter had this mutation and had surgery as baby

T-Box gene: Mesoderm/germ layer development, specifies which limbs will be upper/lower, helps create symmetry for body

Helix-Loop-Helix proteins: Common in TF’s that are involved in myogenesis (muscle tissue formation)

Question 4

Describe zinc finger transcription factors

Answer 4

• Regularly placed cystidine and histidine bound by zinc ions-finger structure
• Regulate myogenesis
• Bone, cartilage, teeth development
• Zn deficiency: skeletal growth retardation, risk factor in osteoporosis

Question 5

Describe signaling molecules and compare TGF-β, FGF, Hedgehog and Wnt families.

Answer 5

TGF-β: (Transforming growth factor) Role in embryogenesis and postnatal life, variety of formation, structure and modification

FGF: (Fibroblast growth factors) Role in angiogenesis, wound healing, embryonic development (limbs/brain), endocrine signaling pathways. Tells limb to grow away from body

Hedgehog: Does a TON. Determining of body/face, organization of brain

Wnt: role in Gastrulation and organogenesis (in cell to cell movement), leads to tons of problems

Question 6

Explain how a signaling molecule can function as an inhibitor.

Answer 6

Can inhibit other signaling molecules.

• SHH/FGF: positive regulators of growth
• BMP: negative regulator of growth. (BMP4: blocks neural formation, and so other signaling molecules(noggin, chordin) block BMP4 so neural plate can form)
• Normal development requires a balance

Question 7

Describe the role of receptor molecules in development. Where are they most commonly located?

Answer 7

Bind to signaling molecules

Receptors for lipid soluble molecules (steroids, retinoids, thyroid hormones) are intracellular

Ex. Notch receptor: very basic, preserved unchanged throughout animal kingdom

Question 8

Describe the role of vitamin A and retinoic acid in embryonic development.

Answer 8

Metabolite of Vit A

Helps determine position along anterior/posterior during development (acts as signaling molecule)

Acts through HOX genes

Too much: turns posterior–>anterior

Question 9

Describe the relationship between proto-oncogenes and tumor suppressor genes and cancer

Answer 9

Proto-oncogenes: upon activation, become a tumor-inducing agent, an oncogene

Tumor suppressor: normally suppress cell division

Ex. Abnormal PTCH no longer inhibits SMO–>uncontrolled SMO activity–>sends signals and genes are instructed to grow

**PTCH mutation is the basis for basal cell carcinoma.

Question 10

Role of Sox genes

Answer 10

Subset of Zing Fingers

Bind to minor groove (has HMG-box sequence)

SoxA=SRY-sex determining region of Y chromosome (males didn’t look male)

Mutations=wide variety

Ex. Sox9: campomelic dysplasia (short legs, club feet, bone abnormalities, ambiguous genitalia, can’t keep trachea/larynx open (laryngeotracheal)

Question 11

HOX genes

Answer 11

HOX genes: “head to tail development”, regulated by retinoic acid (Vit A), HOX genes lay out big pattern and retinoic acid makes boundaries

Question 12

Pax genes

Answer 12

Pax: Early formation of organs, tissues. CNS/sense organs, pancreas, maintaining normal function of certain cells after birth

Question 13

Lim proteins

Answer 13

Lim proteins: Formation of all body segments, absence can lead to headless mammalian embryos, like HOX-big pattern development

Question 14

Dlx genes

Answer 14

Dlx genes: role in outgrowing appendages in early embryogenesis, shaping of jaws and inner ear

Question 15

Msx genes

Answer 15

Msx genes: -prenatal- inhibitors of cell differentiation

• Post-natal: help tissues to keep dividing
• Involved w/ bones on skull, face and limbs
• Teachers daughter had this mutation and had surgery as baby

Question 16

T-Box gene

Answer 16

T-Box gene: Mesoderm/germ layer development, specifies which limbs will be upper/lower, helps create symmetry for body

Question 17

Helix-Loop-Helix proteins

Answer 17

Helix-Loop-Helix proteins: Common in TF’s that are involved in myogenesis (muscle tissue formation)