TF Regulatory Mechanisms Flashcards
Which two morphogens act on patterning the D-V axis by secreting morphogen from the dorsal side of the neural tube?
BMP and Wnt
Once morphogen gradients are established, describe how responding cells are “locked in” to a cellular program
Once a cell reacts to a morphogen and its cellular fate is determined, downstream target genes of the morphogen are activated and the cell can continue on this path independently of its exposure to a morphogen
Define a coherent feedforward loop
In a pathway x, y, z, the pathway from x > y > z is the same sign as the path from x directly to z
Define an incoherent feedforward loop
The sign of path X to Z is the opposite of the sign of the path from X to Z through transcription factor Y
What is the functional importance of incoherent feedforward loops? (3)
- can generate temporal pulses of Z response
- accelerate the response time of z
- act as a band-pass amplitude filter providing maximal Z activity for intermediate x activity
What types of variables affect feedforward loops? (3)
concentrations of x, y and z
time
post-transcriptional mechanisms
what is the advantage of a double-negative gate over direct activation from x > z?
More locations for regulation, and more control over the overall mechanism - can directly turn Z on and off instead of indirectly turning Z off
Describe the fruit fly antennapedia mutation
Legs develop where antennae should be
Define a homeotic selector gene
A gene which determines the positional identity of a segment
Who coined the term homeosis. Define homeosis
William Bateson in 1894 - definition: a being made like, resemblance
Describe the chromosomal organization of hox genes
They appear on the chromosome ordered as they would be expressed along the AP axis (anterior genes first for head, posterior genes last for feet)
In flies there are two major homeotic gene complexes, what are they called?
Antennapedia complex, bithorax complex
What are the 4 very general regions of the fly larval cuticle from most anterior to most posterior
Head (acron), thorax, abdomen, telson
The anterior hox genes in flies are located at the (5’, 3’) end of the chromosome
5’
Describe the common mechanism which prevents mutations such as the antennapedia mutation
Normally other genes repress hox genes dedicated to other body segments
Homeotic selector genes are sometimes also called…
Realisator genes
All homeodomain genes have… What is this motif called?
A 60 aa conserved region called the homeodomain
The homeodomain area of a gene codes for…
Transcription factor
Genes with homeodomains are called
Homeobox genes
Approximately how many homeobox genes are there in humans?
235
Describe the anatomy of the homeobox
3 alpha helix region where TFs bind
What is the core binding sequence on DNA to which homeobox proteins bind?
TAAT
Homeodomain sequence specificity is achieved at this location…
The 9th amino acid of helix 3
Flies have the Hom-C cluster of homeodomain genes. How many paralogous clusters exist in mammals? Why do mammals have more of these?
4 clusters
Have them from random gene duplication at some point in evolution
Of the 4 paralogous hox gene clusters that mammals have (hom-C in flies), what regions of the gene are particularly conserved among all paralogous genes in mammals?
10 and 11 regions - may have some regulatory role which has promoted conservation
What hox gene inhibits the formation of the thoracic skeletal region in mice?
Hox10
What hox gene inhibits the formation of the lumbar skeletal region in mice?
Hox11
Describe the relationship between the sacral, lumbar, and thoracic skeletal regions and the hox genes which inhibit the formations of these regions
thoracic formation inhibited by hox10, lumbar inhibited by hox 11, when both are inhibited the region becomes sacral
Describe hox gene expression within a limb: how are the genes represented along the chromosome?
They are ordered in sequence as they are expressed on the limb
Mutations in Hoxa11 and Hoxd11 (the only two hox genes in the zeugopod region) in mice results in…
Complete loss of the ulna and radius (the bones of the zeugopod area)
During the initial stages of development, hox genes are…
globally silent
Describe the activation of hox genes
They are activated progressively and directionally (e.g. posterior to anterior in deuterostomes) - this sequence of activation is the same sequence as the genes appear on the chromosome
Define temporal colinearity
The activation of hox genes in sequence from posterior to anterior as development progresses
The expression pattern reflected by temporal colinearity is largely activated through changes in…
Epigenetic expression
What are the 2 main ways histones are modified?
Modifications of histone proteins occur at lysine 27 (inactive) or lysine 4 (active) - the area in which you have trimethylation of these residues will dictate whether your transcription factor is active or inactive
Histone proteins make up a (1)-mer
Octamer
What is the role of median motor column (MMC) neurons?
Span the whole SC, contain MN that project to axial muscles
What is the role of hypaxial motor column (HMC) neurons?
Span the thoracic levels, innervate the body wall muscles
What is the role of lateral motor column (LMC) neurons?
Contain motor neurons that innervate the limbs
What is the role of preganglionic motor column (PGC) neurons?
Contain visceral motor neurons which innervate sympathetic ganglia
The PGC neurons are a division of this subset of the nervous system
Autonomic
The PGC neurons regulate…
Bodily functions and fight or flight response
The PGC neurons are located in this region of the SC
thoracic
In the chick, the PGC neurons are also called…
The Column of Terni (CT) neurons
