Molecular Patterning During Development

Question 1

Potency

Answer 1

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

Question 2

Totipotent

Answer 2

Cells of the very early mammalian embryo; identical and unrestricted; can give rise to any cell of the body (EMBRYONIC)

Question 3

Pluripotent

Answer 3

Inner cells of the blastocyst; less potent; can give rise to many cell types but not all (EMBRYONIC)

Question 4

Multipotent

Answer 4

Blood stem cells;

they give rise to cells that have a particular function (ADULT)

Question 5

First stage: of commitment

Answer 5

specification (reversible)
Capable of differentiating autonomously if placed in isolation BUT can be respecified if exposed to certain chemicals/ signals.

Question 6

Second stage: of commitment

Answer 6

determination (irreversible)

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

Question 7

Intrinsic signal method of specification

Answer 7

cell autonomous signal tells the cell ‘who is it’

Question 8

Extrinsic signal method of specification

Answer 8

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

Question 9

when is a cell said to be ‘determined’

Answer 9

When a cell “chooses” a particular fate

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

Question 10

Competence

Answer 10

ability of a cell to respond to the chemical stimuli.

Question 11

Bivalent chromatin

Answer 11

Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region

Question 12

Intramembraneous ossification

Answer 12

he formation of bone in fibrous connective tissue (which is formed from condensed mesenchyme cells)
The process occurs during the formation of flat bones such as the mandible and flat bones of the skull

Question 13

HOX Genes Pattern the body axis

Answer 13

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

Question 14

Limb Development

Answer 14

During embryonic development HOX genes determine the body axis and the position of the limbs along the body axis - Intrinsic factors:
The products of HOX genes belong to a class of proteins known as transcription factors, which bind to DNA, and thereby regulate the transcription of other genes (e.g. TBX5, TBX4).

Question 15

Once the cranio-caudal position is set, limb growth is regulated along three axes:

Answer 15

1. Proximo-distal axis

2. Antero-posterior axis 3. Dorso-ventral axis

Question 16

Upper Limb buds appear on approximately day

Answer 16

24 between somites C5-T1

Question 17

Lower limb buds appear on approximately day

Answer 17

28 between somites L1-S2

Question 18

Rotation of the Limbs

Answer 18

• Development of fore and hind limbs is similar
• In week 7 the forelimbs rotate 90° laterally and the hind limbs
rotate 90 ° medially.
• Results in the flexor compartments being anterior in the upper limb
and posterior in the lower limb

Question 19

Limb Bud consists of:

Answer 19

• Core of mesenchyme derived from parietal layer of lateral plate mesoderm
• Ectoderm which forms the outer covering of the limb (epidermis)
• Ectoderm is thickened at the ‘apex’ of the developing limb to form the Apical Ectodermal Ridge (AER)

Question 20

1 AER controls proximo-distal development

Answer 20

The AER is a key structure in limb development
• It induces the underlying tissue to remain as a
population of undifferentiated, rapidly proliferating cells- known as the PROGRESS ZONE
• As cells move further away from the AER they will begin to differentiate into cartilage and muscle
• This differentiation results in proximo-distal development
2 Initiation of outgrowth of the fore limb is
controlled by the TBX5 gene and FGF-10
3 AER secretes FGF4 and FGF8 to maintain the progress zone and the further development of the proximo- distal axis
4 As growth progresses, mesenchymal cells are left behind the advancing ridge (and its influence) and so they begin to differentiate

Question 21

2 ZPA controls the antero-posterior axis (Cranio-caudal axis)

Answer 21

The antero-posterior axis iiis regulated by the Zone of Polarizing Activity (ZPA)
Cluster of cells near the posterior border of the limb form the ZPA which regulates the AP axis
It ensures that the thumb grows on the cranial (anterior) side of the limb bud
ZPA expresses the protein sonic hedgehog (SHH). ZPA moves distally with the AER
Expts. in chicks show that adding a ZPA to the limb bud results in mirror image duplication of digits

Question 22

3 Dorso-ventral axis

Answer 22

BMPs in the ventral ectoderm
induce EN1
EN1 represses WNT7 restricting its expression to the dorsal limb ectoderm
WNT7 induces LMX1 which then specifies the cells to be dorsal
dorsal

Question 23

Amelia

Answer 23

complete absence of the limbs

Question 24

Meromelia

Answer 24

partial absence of the limbs

Question 25

Phocomelia

Answer 25

absence of long bones

Question 26

Micromelia

Answer 26

segments are abnormally short

Question 27

Holt Oram Syndrome

Answer 27

Holt Oram Syndrome-TBX5 mutations lead to defects in limb development
Upper limb deformities, heart defects