Limb Development Flashcards
Define cell differentiation.
Process by which embryonic cells become
different from one another, resulting in the emergence of cell types such as muscle, nerve, skin and fat cells. It
is the achievement of a stable terminal state (not just transitory differences) and is characterized by the profile of proteins in that cell.
Identify principles governing cell differentiation.
-Generative program: The embryo does NOT contain a description of the adult, rather it contains a generative program for making it (progressive series of instructions).
-Regulatory proteins work together as 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
Identify the main cell stages following fertilisation.
- Morulla (TOTIPOTENT cells, can become any tissues, including placenta)
- Blastocyst (inner cell mass made of PLURIPOTENT cells, can become any tissue except placenta + trophoblast which form placenta)
- (this only applies to cells derived from inner cell mass) Multipotent blood stem cells (can develop into more than one cell type like RBCs and WBCs, but are more limited than pluripotent cells) and other stem cells (e.g. for muscle, or for bone, etc.)
Define Potency, totipotent, pluripotent, multipotent.
Entire repertoire of cell types a particular cell can give rise to in all possible environments.
• Totipotent (toti= whole).
Identical and unrestricted; can give rise to any cell of the body (EMBRYONIC) (e.g. Cells of the very early mammalian embryo)
• Pluripotent (pluri= more).
Less potent; can give rise to many cell types but not all (EMBRYONIC) (e.g. Inner cells of the blastocyst)
• Multipotent (multi= many)
Give rise to cells that have a particular function (ADULT) (e.g. Blood stem cells;)
Define cell fate.
The fate of a cell describes what it will become in the course of normal development.
When a cell “chooses” a particular fate, it is said to be determined, although it still “looks” just like its undetermined neighbours. Determination implies a stable change - the fate of determined cells does not change.
Describe two stages of commitment (and briefly what happens before that).
First, cell is naive.
- SPECIFICATION (reversible)
Capable of differentiating autonomously if placed in isolation BUT can be respecified if exposed to certain chemicals/ signals. How it becomes specified:
-Intrinsic signal – cell autonomous signal tells the cell ‘who is it’
-Extrinsic signal -a chemical or molecule in the environment gives the cell spatial information, tells the cell ‘where it is’ - Determination (irreversible)
Cell will differentiate (i.e. acquire cell specific gene expression) autonomously even when exposed to other factors or placed in a different part of the embryo (competence for alternative fates lost).
Define competence of a cell. How can a cell lose competence.
Ability of a cell to respond to the chemical stimuli.
A cell can lose competence by changes in surface receptor or intracellular molecules
Explain how gene expression changes underlie
cell differentiation/the mechanistic basis of fate decision.
“1. Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation (genes both active and silenced)
- When an ES cell receives a signal to differentiate into a specified cell lineage, activation of the specific developmental genes are needed for differentiation. The developmental genes needed will be activated and the other genes that are not required for that cell lineage will be repressed (silenced) through their bivalent domains.
- After the differentiation has taken place, genes needed for differentiation may be silenced (because no longer needed).”
- Developmental regulatory genes such as HOX, SOX, T-box are associated with transcription factors (which can be stimulatory or inhibitory, balance of the two determines how strongly the gene is expressed) which bind upstream to promoter regions and act as developmental regulators. They bind to these regulatory sequences and help differentiate some cells down particular lineage.
- Combinations of a few regulatory proteins can generate many cell types
At which cell stage can see some features change within cells to do with cell date decision ?
4 cell stage
Identify a situation where it is possible to turn determined state back.
Experimentally, can reverse that locked in pattern, take terminally differentiated cells and turn them back
into embryonic stem cells. Through Somatic Cell Reprogramming (by defined factors or therapeutic cloning)
Explain the embryonic development of the somites, myotomes and dermatomes.
Somite formation occur as paraxial mesoderm becomes segmented.
- Cells of paraxial mesoderm have an internal clock
- They go through cycles every 90 minutes defined by notch signalling clock
- Wave of signal passes through the embryo
- When the wave passes cells, they are programmed to change into part of a somite
- If the wave passes cells early in the cycle, they become the front end of the segment (head end)
- If the wave passes cells late in the cycle, they become the tail end of the segment
- Process repeated over and over
- myotome is the part of a somite that develops into the muscles
- dermatome is the part that develops into skin
Identify and define the processes of growth and ossification of fetal bones taking place in fetal development.
- Endochondrial Ossification
- Uses hyaline cartilage as the model for long bone formation.
- Radiologists can determine the skeletal age of a patient by examining the development of epiphyseal plates - Intramembraneous Ossification
- 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
Define mesenchyme.
Generalised embryonic connective tissue derived from mesoderm
Describe the location and function of HOX genes.
-where: expressed along the long axis of the embryo from head to tail
-function: determine the body axis + the position of the limbs along the body axis + the shape of bone
(products are transcription factors which bind to DNA, and thereby regulate the transcription of other genes (e.g. TBX5, TBX4))
Describe the process of development of limbs (not the role of genes in it, the process itself).
- Upper Limb buds appear on approximately day 24 between somites C5-T1
- Lower limb buds appear on approximately day 28 between somites L1-S2
-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
• The sole of the foot is equivalent to the palm of the hand and big toe (hallux) is equivalent to the thumb (pollux)
-By week 8 all major components of the limbs are present and medial rotation of the LL is complete
