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1. What is a transcription factor?
- Proteins
- → binds to specific DNA sequence
- → regulates gene expression by promoting or suppressing transcription
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1. What is the first step in the action of transcription factors?
- Some kind of signal activates the transcription factor
- Examples:
- hormone in/out of the cell
- build up of secondary messengers
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1. What else might be needed to make a transcription factor active?
- Cofactors
- -hormones can act as cofactors
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1. Following activation of the transcription factor, what happens?
- Cascade to switch many proteins on or off
- → different genes can have the same sequence so can all be affected by the same TF
- → some may be switched on while others may become switched off
- → In this way genes can be controlled as a unit
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1. What mechanisms do transcription factors have of gene control?
- Bind near transcription start site and help form the transcription initiation complex
- Bind to regulatory sequences which may be up or downstream from the gene to be contolled
- Can alter polymerase access to the gene altering transcription
- Can help to recruit or inhibit transcriptional machinery
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1. How are TFs involved in cell differentiation?
- Growth factors activate TFs
- → These alter expression of multiple genes
- → Resulting in different protein expression
- → This then allows differentiation
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1. How do TFs indirectly affect the expresson of genes?
- Start a cascade
- → may control the transcription of a gene which is itself coding for transcription factors
- → these then regulate other genes allowing the initial TF to indirectly be a cause
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2. What are Hox genes?
- Group of related genes that encode the Hox proteins
- → specify regions of the body along head-tail axis
- → ensure correct structures form in correct places (e.g. wings on right segment)
- → confer segmental/positional identity but do NOT form the segments themselves
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2. What are the Hox proteins?
- Transcription factors
- → switch on cascades of genes at different times
- Homeodomain: - binding region of the protein specific to DNA
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2. What levels can Hox proteins act at?
- "executive" level: regulate genes which in turn regulate large networks of other genes
- → e.g. the gene pathway that forms an appendage
- directly regulate realisator genes at the bottom of hierarchies
- → ultimately forming tissues, structures and organs of each segment
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2. What are somites?
- divisions of the embryo
- form in cranio-caudal direction (?)
- form structures such as the vertebrae, rib cage, skeletal muscles, cartilage, tendons and skin of back
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2. How do the Hox proteins specify the somites?
- They specify the pre-somitic mesoderm before somitogenesis
- → when somites form the are specified based on the region of mesoderm from which they develop - along the head-tail axis
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2. What processes does segmentation involve?
- Morphogenesis → differentiation of precursor cells to their terminal specialised cells
- Tight association of cells with similar fates
- Sculpting of structures and segment boundaries → programmed call death and movement of cells from site of birth to site at which they will function
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2. What processes do the target genes of Hox genes affect?
- Promote cell division
- Cell adhesion
- Apoptosis
- Cell movement
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3. Describe the process of neurulation.
- 1. Gastrulation forms 3 germ layers - Ectoderm, Mesoderm, Endoderm
- 2. Ectoderm differentiated to form Epidermis and Neural Ectoderm
- - Notochord secretes Noggin (antagonist of BMP4) allowing the mid-region to execute the neural pathway
 - 3. The neural ectoderm thickens centrally becoming the neural plate
- 4. Hinge point forms down the midline of the neural plate which begins folding inwards
- 5. The ectoderm pushes laterally causing the neural folds to eventually meet and fuse forming the neural tube
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3. What does the neural tube eventually form?
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3. Which portion of the neural tube forms the brain?
Anterior
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3. When do the brain vesicles arrise?
Shortly after neural tube closure
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3. What are the three primary brain vesicles?
- Forebrain: Prosencephalon
- Midbrain: Mesencephalon
- Hindbrain: Rhombencephalon
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3. What are the secondary brain vesicles and where do they arise from?
- Prosencephalon produces:
- - Telencephalon
- - Diencephalon
- Rhombencephalon produces:
- -Metencephalon
- -Myelencephalon
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3. What do the different brain vesicles go on to become?
- Telencephalon: Cerebrum
- Diencephalon: Hypothalamus, thalamus etc.
- Mesencephalon: Mid-brian
- Metencephalon: Pons and Cerebellum
- Myelencephalon: Medulla oblongata
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3. What is the long name for Pax6? What is it encoded by?
- Paired box protein 6
- PAX6 gene in humans
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3. What are the general roles of Pax6?
- Regulates gene transcription
- Acts as a potent cell fate determinant
- Often affects cell proliferation
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3. What is a specific example of Pax6 during brain development?
Pax6 (and other factors such as Pax2) play a role in defining the boundary between the prosencephalon and mesencephalon during the neural plate stage.
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3. How does Pax6 work as a transcription factor?
- Has two DNA binding domains which regulate specific functions of Pax6
- → PD (Paired Domain)
- → HD (Paired-type homeodomain)
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3. How do the two domains of Pax6 work together?
- Both have specific DNA binding sites
- May influence each other's binding
- May cooperate on binding
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3. What is the primary role of the HD?
Important in the developing eye
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3. What is the primary role of the PD?
- (EXAMPLE) PD has a predominant role in dorso-ventral patterning of the telencephalon
- HD has a very subtle role here
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