Molecular patterning in development Flashcards
What is cell differentiation?
Process by which embryonic cells become different from one another
What is potency?
Entire repertoire of cell types a particular cell can give rise to in all possible environments
What is a totipotent cell?
Identical and unrestricted, they can give rise to any cell
• Embryonic
• e.g. cells of the very early mammalian embryo
What is a pluripotent cell?
- Can give rise to many types of cell but not all
- e.g. inner cells of blastocyst
- Embryonic
What is a multipotent cell?
- Can give rise to cells with a particular function
- e.g. blood stem cells
- Adult
What are the two stages of commitment?
1) Specification (reversible)
• When the cell is capable of differentiating autonomously if placed in isolation but can be respecified if exposed to certain chemicals/signals
2) Determination (irreversible)
• Cell will differentiate autonomously even when exposed to other factors or placed in a different part of the embryo
How does a naive cell become specified?
- Intrinsic signals: Cell autonomous signal tells the cell ‘who it is’
- Extrinsic signal: chemical or molecule in the environment gives the cell spatial info, tells the cell where it is
What is a determined cell?
Cell has chosen its fate- fate doesn’t change, it looks like all of its neighbouring undetermined cells
What are the stages of a cell becoming differentiated?
- Naive (experiences cytoplasmic determinants or induction)
- Specified (experiences a loss of competence for alternative fates)
- Determined cell (experiences cell specific gene expression)
- Differentiated
What is competence?
The ability of a cell to respond to chemical stimuli
How can a cell lose competency?
Changes in cell surface receptors or intracellular molecules
Describe the chromatin I poised cells
Both closed and open bivalent chromatin
What are the developmental regulator genes?
- HOX
- SOX
- T-box
Describe the stages of somatic cloning
1) Isolate cells from the patient
2) Remove the nucleus from an egg cell
3) Transfer the nucleus from a patients cell to the egg
4) Egg cell reprograms the patients DNA
5) Stimulate the cell to begin dividing, let it develop to the blastocyst stage
6) Isolate the inner cell mass, grow in a dish
Describe the stages of somatic cell reprogramming (IPS)
1) Isolate cells from patient (skin or fibroblasts); grow in a dish
2) Treat cells with ‘reprogramming factors’
3) Wait
4) Induced pluripotent cells
5) Change culture conditions to stimulate cells to differentiate into a variety of cell types
What is intramembranous ossification?
The formation of bone in fibrous connective tissue (formed from condensed mesenchyme cells)
What is mesoderm?
One of the early embryonic germ layers: ectoderm, mesoderm, endoderm
What is mesenchyme?
Embryonic connective tissue derived from mesoderm
What are HOX genes?
Related group of genes expressed along the head-tail axis of embryo from head to tail
• Determine the body axis
• Determine the position of limbs along the axis
Once cranio-caudal position is set, what 3 axes is limb growth regulated along?
1) Proximo-distal
2) Antero-posterior
3) Dorsal-ventral
When do upper limb buds form and where?
approx 24 days
C5-T1
When do the lower limb buds form and where?
Approx 28 days
L1-S2
Which direction do each of the limbs rotate?
- upper= laterally
* Lower = medially
What does a limb bud consist of?
- Core of mesenchyme
* Ectoderm - thicket at apex to form the apical ectodermal ridge
How is the proximo-distal axis regulated?
- Apical Ectodermal Ridge (AER)
- Induces the underlying tissues to remain as a population of undifferentiated, rapidly proliferating cells - the progress zone
HOX 8
Controls the position of the limbs on the long body axis
TBX 5
Controls the initiation of outgrowth of the forelimb with FGF 10
What does the AER secrete and what is the effect
- FGF-4 and FGF-8
* Maintains the progress zone and further development of the proximo-distal axis
What regulates the antero-posterior axis?
Zone of Polarizing Activity (ZPA)
• Formed by a cluster of cells near the posterior border of the limb
What does the ZPA do?
- Ensures the thumb is on the cranial side of the limb bud
* Expresses the protein Sonic Hedgehog (SHH)
What happens in limb development if ZPA is added to the limb bud?
Mirror image duplication of digits- fingers but no thumbs
What is the Antero posterior axis on the hand?
Thumb to little finger
How is Dorso ventral axis controlled?
- BMPs (bone morphogenic proteins) in the ventral ectoderm induce EN1
- EN1 represses WNT7, restricting its expression to the dorsal limb ectoderm
- WNT7 induces LMX1 which then specifies the cell to be dorsal
What is the expression of HOX genes dependent on?
- SHH
- FGF
- WNT7a
Upper limb gene
TBX5
Lower limb gene
TBX4
Syndactyly
Apoptosis doesn’t occur- webbed hands or feet
Amelia
Complete absence of limbs
Meromelia
Partial absence of the limbs
Phocomelia
Absence of long bones
Micromelia
Segments are abnormally short
Thalidomide
Interaction with one of the axes
Caused Amelia and phocomelia
Holt Oram syndrome
TBX5 mutation
• upper limb deformities
• Heart defects
Brachydactyly
Short digits
Syndactyly
Fused digits-failure of apoptosis
Polydactyly
Extra digits
Cleft foot
Lobster claw deformity
