Lecture 19. Cellular Response to Positional Information: The Hox Code Flashcards

1
Q

How do cells respond to positional information ?

A
  1. Cell division
  2. Cell differentiation
  3. Changes in cell shape
  4. Changes in cell movement
  5. Apoptosis
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2
Q

What is a tell - tale sign for when a gene is switched on in a eukaryotic cell ?

A

The presence of mRNA specific for the gene within the cell

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3
Q

What are the methods for detecting gene expression ?

A
  1. Transcriptomics
  2. RT-PCR amplification from mRNA
  3. In situ hybridisation
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4
Q

What is in situ hybridisation ?

A

The approach that allows examination of gene activity in both time and space in the embryo

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5
Q

What is in situ hybridisation based on ?

A

Detecting mRNA within cells within the whole embryo.

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6
Q

How does in situ hybridisation work ?

A

A labelled probe is generated that has a sequence complimentary to the mRNA and can bind tightly to it. The probe can be visualised by a stain or can be made fluorescent

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7
Q

How might a cell respond to positional information ?

A
  1. Proliferate
  2. Change gene expression - differentiate
  3. Change cell shape
  4. Move - migrate
  5. Apoptosis
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8
Q

What can stimulate proliferation ?

A

Mitotic factors

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9
Q

What is proliferation ?

A

The division of cells to form new cells

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10
Q

Is cell proliferation highly controlled ?

A

Yes highly controlled at all stages

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11
Q

What do most cancers derive from ?

A

Mutations that give rise to a single abnormal somatic cell where cell division and growth go unchecked

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12
Q

What is cell differentiation brought about by ?

A

Change in gene expression

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13
Q

What sort of process is cell differentiation ?

A

Its a progressive, multilayered - receipt and response to multiple signals

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14
Q

What do specialised cells produce in cell differentiation ?

A

Proteins tailored to their specialised function

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15
Q

What are the specialised proteins in red blood cells ?

A

Haemoglobin

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16
Q

What are the specialised proteins in epidermal cells ?

A

Keratin

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17
Q

What are the specialised proteins in neurons ?

A

Voltage gated ion channel

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18
Q

What are the specialised proteins in muscle ?

A

Specific actin and myosin proteins

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19
Q

What causes localised contraction of particular cell ?

A

Contraction of cytoskeleton elements

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20
Q

What does cell motility do ?

A

Trigger the cell to move

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21
Q

What is cell motility brought about by ?

A

Changes in cytoskeleton

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22
Q

How do cell crawl in cell motility ?

A

Production of filopodia or lamellipodia

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23
Q

What do cells need to allow cell motility ?

A

Dismantle cell adhesion proteins

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24
Q

What can cell only move through ?

A

A receptive environment

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25
Q

As a result of cells only being able to move through a receptive environment what happens ?

A

They will be attracted or repelled depending on the extra cellular matrix of neighboring cells

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26
Q

What is blastocoel inside the gastrulating embryo rich in ?

A

Fibronectin

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27
Q

What is fibronectin ?

A

An attractant that encourages internal migration

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28
Q

What is apoptosis ?

A

Cell elimination by programmed cell death

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29
Q

How does apoptosis work ?

A

The cell is induced by an external or internal signal to fragment its DNA and to shrink, without release of the cell contents

30
Q

Where is apoptosis common ?

A

Widespread in development where cells need to be removed to sculpt the right shape and structure

31
Q

Where was apoptosis discovered ?

A

C. elegans

32
Q

What carries out apoptosis ?

A

Caspases

33
Q

What carries out apoptosis in nematodes ?

A

CED-3

34
Q

What carries out apoptosis in mammals ?

A

Caspase - 9

35
Q

What does the lack of caspase 9 result in ?

A

Loss of apoptosis, disrupting in normal brain development due to too many neurons

36
Q

What is apoptosis present in ?

A

Homeostasis

37
Q

What are the three categories if genes that build the body plan ?

A
  1. Maternal effect gene
  2. Segmentation genes
  3. Homeotic genes
38
Q

What does maternal effect gene do ?

A

Set up the major axes of the embryo (anterior posterior and dorsal ventral) early in development

39
Q

What does the segmentation gene do ?

A

Divide the embryo into segments along the anterior posterior axis

40
Q

What does the homeotic gene do ?

A

Determine segment identity

41
Q

What do mutations in homeotic genes do ?

A

Structure characteristic of a particular part arising in the wrong place

42
Q

What does a molecular analysis of homeotic genes show ?

A

That they encode cell specific transcription factors

43
Q

What does the combination of homeotic genes express in any segment confer ?

A

Identity

44
Q

What were homeotic genes found to be ?

A

Similar to each other and are clustered in the genome

45
Q

Where are homeotic genes expressed ?

A

In a sub set of segments in the embryo where they contribute to segment identity

46
Q

What is colinearity ?

A

Position of the gene in the cluster reflects the position along the anterior posterior axis where the gene is expressed

47
Q

What are the known as the hox genes ?

A

Clustered genes, that determine the identity of structures in the embryo and clustered in the genome

48
Q

What is the function of cell specific transcription factors ?

A

Bind to specific sequences in the control regions of a gene, and switch on or off gene expressions

49
Q

What are homeotic genes ?

A

When mutated show phenotypes where structures appropriate to one part of the body plan appear elsewhere

50
Q

Who originally studied drosphilia body plans ?

A

Ed Lewis

51
Q

What is a homeobox ?

A

A 180bp conserved DNA sequence found in a family of cell specific transcription factors

52
Q

What is the homeodomain ?

A

60 amino acid within the resulting protein encoded by the 180bp conserved sequence.

It forms a helix-turn-helix structure in the protein that binds to DNA in a sequence specific manner - the protein is a cell specific transcription factor

53
Q

What are the hox genes ?

A

Homeotic genes that contain a homeobox sequence that encodes a homeodomain transcription factor

54
Q

What are hox genes a subset of ?

A

All homeobox genes particularly involved in positional identity

55
Q

What must animals have in order to have genes similar to hox genes ?

A

Organised body plan

56
Q

How many clusters are there in mammals ?

A

4

57
Q

What is the advantage of having four clusters of hox genes ?

A
  1. DNA sequence is conserved

2. Chromosomal arrangement of the gene is conserved

58
Q

What does removal of multiple hox genes in vertebrates result in ?

A

A much more dramatic mutant phenotype

59
Q

What happens when hoxc8 is mutated in mice ?

A

An extra thoracic vertebra with ribs is formed, vertebrae being produced in one position that are appropriate to another position

60
Q

How do hox genes function ?

A

By conferring a complicated positional code called the hox code

61
Q

What is the structure of hox genes in humans and mouse ?

A

There are 39 hox genes arranged in four clusters

62
Q

How are the hox genes expressed in the mouse and human ?

A

Arranged in overlapping domains along the anterior posterior axis of the embryo

63
Q

What do hox transcription factors regulate ?

A

Development by coordinating the transcription of batteries of other developmental genes

64
Q

What are the features of the hox genes ?

A
  1. They contain a sub class of highly conserved homeobox, so they encode transcription factors
  2. They are involved in organising the body plan of an animal
  3. They exist in clusters of similar genes in the genome
65
Q

Where are the hox gene expression turned on in the vertebrate limb ?

A

Overlapping domains along the developing limb bud

66
Q

Where are the genes of the hox a cluster expressed ?

A

In overlapping domains along the posterior anterior axis

67
Q

Where are the genes of hox d cluster expressed ?

A

In the overlapping domains along an axis between p/d and a/p

68
Q

What do hox genes pattern ?

A

Both the p/d and a/p axes

69
Q

What does the human mutation HOXD13 cause ?

A

Synpolydactyly

70
Q

What are the A, B and C genes that encode transcription factors ?

A

MADS family transcription factors

71
Q

How many genes and clusters are there in drosphilia ?

A

1 cluster and 11 genes