Molecular Patterning During Development Flashcards
Potency
the entire repertoire of cell types a particular cell can give rise to in all possible environments
Totipotent
Cells of the very early mammalian embryo; identical and unrestricted; can give rise to any cell of the body (EMBRYONIC)
Pluripotent
Inner cells of the blastocyst; less potent; can give rise to many cell types but not all (EMBRYONIC)
Multipotent
Blood stem cells;
they give rise to cells that have a particular function (ADULT)
First stage: of commitment
specification (reversible)
Capable of differentiating autonomously if placed in isolation BUT can be respecified if exposed to certain chemicals/ signals.
Second stage: of commitment
determination (irreversible)
Cell will differentiate autonomously even when exposed to other factors or placed in a different part of the embryo.
Intrinsic signal method of specification
cell autonomous signal tells the cell ‘who is it’
Extrinsic signal method of specification
a chemical or molecule in the environment gives the cell spatial information, tells the cell ‘where it is’
when is a cell said to be ‘determined’
When a cell “chooses” a particular fate
Determination implies a stable change - the fate of determined cells does not change.
Competence
ability of a cell to respond to the chemical stimuli.
Bivalent chromatin
Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region
Intramembraneous ossification
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
HOX Genes Pattern the body axis
Hox genes are a related group of genes that are expressed along the long axis of the embryo from head to tail.
Limb Development
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).
Once the cranio-caudal position is set, limb growth is regulated along three axes:
- Proximo-distal axis
2. Antero-posterior axis 3. Dorso-ventral axis
Upper Limb buds appear on approximately day
24 between somites C5-T1
Lower limb buds appear on approximately day
28 between somites L1-S2
Rotation of the Limbs
• 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
Limb Bud consists of:
- 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)
1 AER controls proximo-distal development
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
2 ZPA controls the antero-posterior axis (Cranio-caudal axis)
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
3 Dorso-ventral axis
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
Amelia
complete absence of the limbs
Meromelia
partial absence of the limbs
Phocomelia
absence of long bones
Micromelia
segments are abnormally short
Holt Oram Syndrome
Holt Oram Syndrome-TBX5 mutations lead to defects in limb development
Upper limb deformities, heart defects
