17 Flashcards
Define paralogs, colinearity, and homeobox as it relates to Hox genes.
Paralogs: genes related by duplication within a genome ex Hoxa1 Hoxb1
Colinearity: the order of genes correlates with the order of its expression (temporal colinearity) in the embryo and the domain of its expression (anterior expression limit, spatial colinearity)
Homeobox: A DNA sequence that codes for a protein domain called a homeodomain (which binds DNA)
What region of a Hox gene’s expression is where its patterning function is most important?
The most anterior region.
What is the difference between a Homeobox and a Hox gene?
A homeobox gene encodes transcription factors with a conserved 60 AA, DNA-binding homeodomain. They also have transactivation, repression, and protein-protein interaction domains. 200+ in the human genome.
Hox genes are CLUSTERED homeobox genes with the same evolutionary origin as Drosophila homeotic complexes - 39 Hox genes.
TLDR: all Hox genes are homeobox genes but not all homeobox genes are hox genes.
Which end of a hox cluster is transcribed first?
The posterior 5’ end.
How are homeodomain sequences related? Are they always identical?
They’re similar but not always identical.
What is an invariant amino acid? Can you list an example?
An invariant amino acid is almost always found at specific locations in any homeodomain. An example is Arginine or Glycine at position 5.
Define posterior prevalence.
The most posterior hox genes tend to have dominant patterning over more anterior 3’ genes, thus they are prevalent.
What is the most anterior region patterned by Hox?
The hindbrain and base of the skull.
What does the homozygous simultaneous loss of function mutation in Hoxa3 and Hoxd3 cause? Is this loss only present when both are knocked out, or just one? Why?
It causes the lost of the atlas, the first cervical vertebrae. The two Hox have overlapping domains of function so both must be knocked out for this to occur.
What happens in the axial skeletons of mice when Hox10 paralogs are all knocked out? How about Hox11?
How about if Hoxa10 gets misexpressed through the whole skeleton?
Hox10: The lumbar region presents thoracic vertebrae because the next most posterior is 9 which patterns thoracic.
Hox11: The sacral region presents lumbar vertebrae because the next most posterior is 10 which patterns lumbar.
Hoxa10 misexp: The gain of function results in all vertebrae above the lumbar region also being lumbar. No ribs.
Describe the technique of making transgenic mice.
A fusion gene construct is created that expresses the gene of interest. This DNA is injected into the pronuclei of a one cell mouse embryo. The DNA is randomly incorporated into the mouse genome. This embryo is transferred to a pseudopregnant mouse. The resulting transgenic mice are bred to other transgenics to establish a line.
What Hox genes code each vertebrae type?
Occipital: Hoxa/b 1-2, Hoxd1
Cervical: Hoxa/b 3-5, Hoxc4-5, Hoxd3-4
Thoracic: Hoxa6,7,9, Hoxb6-9, Hoxc6,8,9, Hoxd8-9
Lumbar: Hoxa/c/d10
Sacral: Hoxa/c/d11
Caudal: Hoxa/b13, Hoxc/d12-13
What does Hoxc6 expression mark in vertebrates?
The anterior limit where the first rib forms (the start of the thoracic region)
Is every Hox paralog required for adequate function?
Not quite! If say you have a vertebrae that needs Hoxc6 and Hoxb6 to develop, one of the two should suffice and you don’t need both.
What are the general trends with Hox loss and gain of function?
Hox loss of function: anterior structures form in a posterior location, which often requires a mutation of ALL members of a paralogous group
Hox gain of function: Only takes one because of posterior predominance, causes posterior structures to form in a more anterior location.
