Developmental Genetics Flashcards
1
Q
What is development?
A
- A progressive change in cell and tissue organisation; changes in cell structure and function,
- Involves the specialisation of tissues and morphogenesis (creation of form)
2
Q
What is a mophogen?
A
- A diffusible molecule (protein) that influences cell fate in a concentration-dependent manner
e. g. Fgf, Wnt
3
Q
What is the early process of drosophila embryo structure development?
A
- Initially after the egg has been fertilised multiple divisions of nuclei occur but no cytokinesis which creates a syncytium (large cell multiple nuclei)
- The nuclei of the syncytium migrate to the edge of the cell and continue to divide
- The nuclei then are enclosed in membranes
4
Q
What is the basic flow of gene hierarchy in the development of the drosophila embryo?
A
- Maternal effect genes:
- TF mRNAs
- set up anterior posterior axis
Zygotic genes-
- Gap genes:
- encode TFs
- expressed in broadly overlapping domains - Pair-rule genes:
- encode TFs
- Divide embryo into modular units (striped expression) - Segment Polarity genes:
- Further divide embryo into 14 sections- define anterior and posterior of each segment
(3+4) = 5. Homeotic selector genes:
- Determine the fate of each segment
5
Q
How do maternal effect genes: bicoid and nanos work?
A
- When an egg is fertilised there are already maternal effect genes (maternal mRNAs) within the egg
- The bicoid mRNA is tethered at the anterior end of the embryo and its products (TFs) diffuse out
- The nanos mRNA is tethered at the posterior end of the embryo and its products (TFs) diffuse out
- These two genes set up a concentration gradient that controls 2 other maternal effect genes: hunchback and caudal
6
Q
How do maternal effect genes: hunchback and caudal work?
A
- These two maternal effect gene mRNA products are laid down evenly across the whole oocyte/embryo
- Bicoid activates the expression of hunchback mRNA and represses caudal
- Nanos activates expression of caudal and represses hunchback
7
Q
How do gap genes work?
A
- These gap genes are controlled by maternal effect gene gradients that are set up when the embryo is still in a syncytium
- The gap genes are activated or repressed by maternal effect genes (and hunchback which is also zygotic) in one or two broad domains across the A-P axis
- The gap gene expression boundaries are also reinforced by repressive interactions between teh gap genes themselves
- The gap genes encode TFs
e. g. expression of the gap gene, Kruppel: - stimulates by bicoid and intermediate levels of hunchback
- inhibited anteriorly by high hunchback and posteriorly by low/no bicoid nor hunchback
8
Q
How do pair-rule genes work?
A
- Pair rule genes respond to upstream maternal effect and gap genes to define their expression boundaries
- Pair rule genes are expressed in seven stripes along the embryo: each stripe is regulated by a different combination of upstream maternal or gap genes (not that factors can be activators or repressors in different stripes)
- When these genes are expressed the embryo is still in syncytium but just starting to segment
e. g. expression of 2nd stripe of even skipped:
- activated by bicoid and hunchback
- repressed by Krupple and Giant
9
Q
What are segment polarity genes?
A
- These act when the embryo is no longerr a syncytium and the there are discrete cells which signal to each other
- Encode transcription factors such as engrailed as well as signalling molecules like wingless and hedgehog
- Expressed in 14 stripes
10
Q
How do segment polarity genes function?
A
- Engrailed is expressed where the pair rule genes eve and Ftz are expressed
- Wingless is expressed in cells where eve and Ftz are not expressed
- This creates expression of wingless (anterior edge of posterior region of segment) and engrailed (posterior edge of posterior region of segment)
- This causes a reciprocal interaction between cells:
1. Engrailed activates hedgehog
2. Secreted hedgehog binds to its receptor patched- this activates smoothened with goes to nucleus and activates certain genes- in particular wingless gene expression
3. Wingless is secreted
4. Wingless binds to Frzld receptor- this stabilised B-catenin which goes into nucleus and activates target genes including engrailed
11
Q
What are homeotic selector genes?
A
- These are genes that provide exact positional information to cells so as to specify the structures that will develop
- They do not directly build structure by provide the key positional info.
- Homeotic selector genes include the Hox genes which are on chromosome 3 and are arranged into an antennapedia complx and a bithorax complex
12
Q
What is a homeotic transformation?
A
- A mutation in which one body part develops as another e.g. antennapedia
13
Q
How many hox clusters are in:
- Drosophila
- Humans
A
- Drosophila: 1
- Humans: 4
14
Q
What hox genes are paralogues?
A
- Genes with the same number have arisen through the genome duplication
e. g. a4, b4, c4 etc.
15
Q
What does co-linearity in terms of Hox genes refer to?
A
- There is co-linearity between expression in embryo and position on chromosome
- genes at the 3’ end such as a1, b1, c1 are expressed earlier in development and more anteriorly
- genes at the 5’ end such as a-10, b-13, d-12 are expressed later and more posteriorly
16
Q
What are the features of homeobox genes?
A
- Homeobox genes can be scattered across the genome or organised into clusters e.g. the four Hox clusters in mammals
- They contain a homeobox which encodes a homeodomain which binds to the major groove of DNA
