1. What is a transcription factor?
- → binds to specific DNA sequence
- → regulates gene expression by promoting or suppressing transcription
1. What is the first step in the action of transcription factors?
- Some kind of signal activates the transcription factor
- hormone in/out of the cell
- build up of secondary messengers
1. What else might be needed to make a transcription factor active?
- -hormones can act as cofactors
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
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
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
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
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
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
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
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
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
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
2. What processes do the target genes of Hox genes affect?
- Promote cell division
- Cell adhesion
- Cell movement
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
3. What does the neural tube eventually form?
3. Which portion of the neural tube forms the brain?
3. When do the brain vesicles arrise?
Shortly after neural tube closure
3. What are the three primary brain vesicles?
- Forebrain: Prosencephalon
- Midbrain: Mesencephalon
- Hindbrain: Rhombencephalon
3. What are the secondary brain vesicles and where do they arise from?
- Prosencephalon produces:
- - Telencephalon
- - Diencephalon
- Rhombencephalon produces:
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
3. What is the long name for Pax6? What is it encoded by?
- Paired box protein 6
- PAX6 gene in humans
3. What are the general roles of Pax6?
- Regulates gene transcription
- Acts as a potent cell fate determinant
- Often affects cell proliferation
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.
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)
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
3. What is the primary role of the HD?
Important in the developing eye
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