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Medicine Year 1 - Semester 2 - Part 2 > Molecular Patterning During Development > Flashcards

Molecular Patterning During Development Flashcards

1
Q

State the principles governing cell differentiation

A

Generative program

Regulatory proteins work together to form a ‘committee’ to control the expression of a eukaryotic gene.

Combinations of a few gene regulatory proteins can generate many different cell types during development.

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2
Q

Describe what the embryo contains

A

The embryo does not contain a description of the adult, rather it contains a generative program for making it.

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3
Q

Cell differentiation

A

Process by which embryonic cells become different from one another.

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4
Q

What does cell differentiation involve ?

A

Involves the emergence of cell types such as muscle, nerve, skin and fat cells.

It is the achievement of a stable terminally differentiated state (not just transitory differences).

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5
Q

How are differentiated cells characterised ?

A

Characterised by the profile of proteins in that cell.

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6
Q

Describe cells just after fertilisation

A

Totipotent
- can form every cell in the body
- placenta too

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7
Q

Potency

A

The entire repertoire of cell types a particular cell can give rise to in all possible environments.

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8
Q

Toti

A

Whole cell

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9
Q

Totipotent

A

Cells of the very early mammalian embryo

Identical and unrestricted

Can give rise to any cell of the body

EMBRYONIC

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10
Q

Describe cells that go on to form the embryo

A

Pluripotent
- Can’t form placental tissues

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11
Q

Pluri

A

More

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12
Q

Pluripotent

A

Inner cells of blastocyst

Less potent

Can give rise to many cell types but not all

EMBRYONIC

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13
Q

Multi

A

Many

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14
Q

Multipotent

A

EXAMPLE:

Blood stem cells

They give rise to cells that have a particular function (e.g. red or white blood cells)

ADULT

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15
Q

Order of stem cells and potency

A

Totipotent
Pluripotent
Multipotent

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16
Q

Commitment

A

Each decision that restricts cell fate
- cells are committed

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17
Q

Key feature of commitment

A

Occurs in 2 stages
1. Specification (reversible)
2. Determination (irreversible)

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18
Q

Describe the 1st stage of commitment

A

Specification (reversible)

Cells are capable of differentiating autonomously if placed in isolation BUT can be respecified if exposed to certain chemicals/ signals.

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19
Q

Describe the 2nd stage of commitment

A

Determination (Irreversible)

Cells will differentiate autonomously, even when exposed to other factors or placed in a different part of the embryo.

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20
Q

How does a naive cell become specified ?

A

Intrinsic and Extrinsic Signals

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21
Q

Intrinsic signals

A

Cell autonomous signal tells the cell ‘who it is’

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22
Q

Extrinsic signal

A

A chemical or molecule in the environment gives the cell spatial information, tells the cell ‘where it is’

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23
Q

Describe cell fate

A

The fate of a cell describes what it will become in the course of normal development.

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24
Q

What does determination imply ?

A

Implies a stable change - the fate of determined cells does not change.

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25
Q

Competence

A

Ability of a cell to respond to the chemical stimuli.

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26
Q

How can a cell lose competence ?

A

A cell can lose competence by changes in surface receptor or intracellular molecules.

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27
Q

Process of a cell during development

A

Naive
Specified
Determined
Differentiated

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28
Q

What happens between naive and specified cell stage ?

A

Cytoplasmic determinants or induction

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29
Q

What happens between the specified and determined cell stage ?

A

Loss of competence for alternative fates

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30
Q

What happens between the determined and differentiated cell stage ?

A

Cell specific gene expression.

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31
Q

Preimplantation

A

Poised genes

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32
Q

Neurogenesis

A

Active genes

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33
Q

Postnatal neurogenesis

A

Silenced genes

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34
Q

Chromatin

A

DNA double helix
Wrapped around histone proteins

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35
Q

What is bivalent chromatin ?

A

Histone features that are part of chromatin.

The mechanistic basis of fate decisions.

ONLY occurs at ‘developmental regulator genes’

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36
Q

Developmental regulator genes

A

Transcription factors that control thousands of other genes.

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37
Q

Bivalent chromatin

A

Histone features that are part of chromatin. - found around the regulator genes.

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38
Q

What happens when bivalent chromatin is expressed ?

A

When they are expressed and make choices, these control big differentiation patterns.

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39
Q

K4

A

GO

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40
Q

K27

A

STOP

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41
Q

Describe embryonic stem cells

A

In embryonic stem cells, which haven’t made any fate choices yet:

You would see both kinds of signal, co-located on these genes.
- Closed pattern
- Open pattern (overlayed at the same time)

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42
Q

Closed conformation tag

A

Corresponds with the gene not being expressed.

43
Q

Poised genes

A

IN bivalent chromatin, the genes are ready to either be expressed or not be expressed.

44
Q

When do fate decisions occur ?

A

Cell fate decisions are made as early as the 4-cell stage.

Decide:
- pluripotent stem cells
- extraembryonic cells to form placenta

45
Q

How are many cell types generated ?

A

Combinations of a few regulatory proteins.

3 regulatory proteins –> 8 different cell types

46
Q

Transcription factors

A

Proteins that bind DNA and regulate thousands of other types of proteins.

e.g. HOX, SOX, T-box families

47
Q

State some developmental regulatory genes

A

HOX
SOX
T-box

(all transcription factors)

48
Q

iPS cells

A

Induced pluripotent stem cells

49
Q

Therapeutic cloning

A

Somatic cell reprogramming

50
Q

Human limb

A

Pentadactyl limb
5 digits

51
Q

Describe the phases of endochondrial ossification

A

Mesenchyme
Cartilage

Osteoblasts and Proliferating chondrocytes

Secondary ossification centre

52
Q

How is skeletal age determined ?

A

Radiologists can determine skeletal age of a patient by examining the development of epiphyseal plates

53
Q

Primary ossification centre

A

Week 12

54
Q

Secondary ossification centre

A

At birth

55
Q

What is intra-membranous ossification ?

A

The formation of bone in fibrous connective tissue (when formed from condensed mesenchyme cells)

56
Q

When does intra-membranous ossification occur ?

A

This process occurs during the formation of flat bones, such as the mandible and flat bones of the skull.

57
Q

What is mesoderm ?

A

One of the early embryonic germ layers.

58
Q

What is mesenchyme ?

A

Mesenchyme generalised connective tissue derived from mesoderm.

59
Q

HOX genes

A

HOX genes are a related group of genes that are expressed along the long axis of the embryo from head to tail.

60
Q

Where have HOX genes been studied ?

A

Drosophila melanogaster

61
Q

Function of HOX genes

A

During embryonic development, HOX genes determine the body axis and the position of the limbs along the body axis - Intrinsic factors.

62
Q

Product of HOX genes

A

Belongs to a class of proteins known as transcription factors that binds to DNA and thereby, regulate the transcription of other genes.

63
Q

State the 3 axis of limb growth

A
  1. Proximo-distal axis
  2. Antero-posterior axis
  3. Dorso-ventral axis
64
Q

Describe upper limb development

A

Upper limb buds appear on approximately day 24, between somites C5-T1

65
Q

Describe lower limb development

A

Lower limbs appear on approximately day 28 between somites L1-S2.

66
Q

When are major components of limbs present ?

A

BY week 8

Also Medial rotation of the LL is complete

67
Q

Describe rotation of the forelimbs and hind limbs

A

In week 7:

  • Forelimbs rotate 90degrees LATERALLY
  • Hind limbs rotate 90degrees MEDIALLY
68
Q

Descriptive terms used in embryology

A

Proximo - Distal
Anterior - Posterior
Dorso - ventral

69
Q

What does rotation of the forelimbs and hind limbs result in ?

A

Results on the flexor compartments being anterior in the upper limb and posterior in the lower limb.

70
Q

What is proximo-distal development controlled by ?

A

Apical Ectodermal Ridge (AER)

71
Q

What is AER ?

A

Ectoderm is thickened at the ‘apex’ of the developing limb, to form the Apical Ectodermal Ridge.

72
Q

What does the limb bud consist of ?

A

Core of mesenchyme - derived from parietal layer of LPM

Ectoderm - forms epidermis

73
Q

Function of AER

A

Controls proximo-distal development

74
Q

Progress zone

A

AER induces the underlying tissue to remain as a population of undifferentiated, rapidly proliferating cells.

75
Q

What happens as cells move further away from AER ?

A

They will begin to differentiate into cartilage and muscle.

This differentiation results in proximo-distal development.

76
Q

Function of HOX-8

A

Controls the position of the limb on the long axis of the body.

77
Q

Function of TBX5 and FGF-10

A

Initiation of outgrowth of the fore limb is controlled by these genes.

78
Q

What does AER secrete ?

A

AER secretes FGF4 and FGF8 to maintain the progress zone and the further development of the proximo-distal axis.

79
Q

What happens as growth progresses ?

A

Mesenchymal cells are left behind the advancing ridge, and so they begin to differentiate.

80
Q

Function of ZPA

A

Controls the antero-posterior axis (from thumb to little finger)

81
Q

ZPA

A

Zone of polarising activity

82
Q

What is the ZPA ?

A

Cluster of cells near the posterior border of the limb.

ZPA regulates the AP axis.

83
Q

What does ZPA express ?

A

The protein sonic hedgehog.

ZPA moves distally with the AER.

84
Q

What genes are involved in the dorso-ventral axis ?

A

BMPs - bone morphogenic proteins

85
Q

Where are BMPs found ?

A

BMPs in the ventral ectoderm, induce EN1.

86
Q

Function of EN1

A

EN1 represses WNT7 restricting its expression to the dorsal limb ectoderm.

87
Q

Function of WNT7

A

WNT7 induces LMX1 which then specifies the cells to be dorsal.

88
Q

Key function of HOX genes

A

HOX genes determine the shape of bones

89
Q

What do variations in the combinations of HOX genes ensure ?

A

Upper and Lower limbs are different:

TBX5 - upper limb
TBX4 - lower limb

Patterns for the proximal, middle and distal hand are defined.

90
Q

What is the expression of HOX genes dependent on ?

A

SHH
FGFs
WNT7a

91
Q

What are limb defects often associated with ?

A

Other abnormalities affecting:

  • CVS
  • GU system
  • Craniofacial structures
91
Q

Syndactyly

A

Failure of programmed cell death of some skin tissue between the digits.

92
Q

Amelia

A

Complete absence of limbs

93
Q

Meromelia

A

Partial absence of the limbs

94
Q

Phocomelia

A

Absence of long bones

95
Q

Micromelia

A

Segments are abnormally short

96
Q

Causes of limb defects

A

Causes may be:

  • Hereditary
  • Environmental (teratogens)
96
Q

Result of limb defects

A

Affects the progress zone with failure of cell division (weeks 4 and 5)

97
Q

Causes of thalidomide

A

Prescribed as a sleeping pill

98
Q

Results of thalidomide

A

Increased incidence of limb abnormalities

Also associated with intestinal atresia and cardiac abnormalities.

Phocomelia or Amelia

99
Q

Holt Oram Syndrome

A

TBX5 mutations lead to defects in limb development

Upper limb deformities –> heart defects

100
Q

Brachydactyly

A

short digits

101
Q

Syndactyly

A

Fused digits
Failure of apoptosis

102
Q

Polydactylyl

A

Extra digits

Medicine Year 1 - Semester 2 - Part 2 (53 decks)

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