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1. Basics concepts of development

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1. Basics concepts of development

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BASIC CONCEPTS OF

DEVELOPMENT
 Embryology: study of development of organism from fertilization

 Development Biology = Embryology + other developments

Objectives of developmental biology:

1. To generate cellular diversity & order within each generation

2. To ensure continuity of life from one generation to another


There are 3 major ways to study developmental biology:

1. Anatomical approach
2. Experimental approach
3. Genetic approach
ANATOMICAL APPROACH

Comparative Evolutionary Teratology Mathematical


embryology embryology Phocomelia modelling
Anatomical changes Homology: common (Thalidomide baby): Isometric Growth: all
during development ancestral origin. Ex: long / absence of parts of body grow at
of different organisms Wing of bird & bat limb bones same rate

Anaology: similar Allometric growth: all


function, different parts of body grow at
origin. Ex: Wing of different rates
bird & insect
Von Baer’s law:
relationships between groups can be discovered by finding common
embryonic or larval forms.

Differentiation:
The development of specialized cell types biochemically &
functionally

Commitment:
When a cell or tissue does not appear phenotypically different but its
developmental fate has become restricted.
Determination:
A cell or tissue is said to be determined when it is capable of
differentiating autonomously even when placed into another region
of the embryo.

TYPES OF COMMITTMENT

Autonomous Conditional Syncytial


Specification/ Specification/ Specification
Mosaic Regulative
development development
AUTONOMOUS SPECIFICATION
 Characteristic of most invertebrates.

 Specification by differential acquisition of certain cytoplasmic molecules present


in the egg.

 Invariant cleavages produce the same lineages in each embryo of the species.
Blasto- mere fates are generally invariant.

 Cell type specification precedes any large-scale embryonic cell migration.

 Produces "mosaic" ("determinative") development: cells cannot change fate if a


blasto mere is lost.
Laurent Chabry study in tunicates
Conklin studies: posterior vegetal pair, B4.1 in the 8-cell tunicate embryo is capable
of producing tail muscle tissue, as it contains the yellow crescent cytoplasm that
correlates with muscle determination.

Whittaker: transferred yellow crescent cytoplasm of B4.1 (muscle-forming) into


b4.2 (ectoderm-forming) of 8-cell tunicate embryo, the ectoderm-forming
blastomere generated muscle cells as well as its normal ectodermal progeny
CONDITIONAL SPECIFICATION
 Characteristic of all vertebrates and few invertebrates.

 Specification by interactions between cells. Relative positions are important.

 Variable cleavages produce no invariant fate assignments to cells.

 Massive cell rearrangements and migrations precede or accompany specification.

 Capacity for "regulative" development: allows cells to acquire different


functions.
EXPERIMENTAL APPROACH

Defect
Experiment

Isolation
Experiment

Recombination
Experiment

Transplantation
Experiment
DEFECT EXPERIMENT
ISOLATION EXPERIMENT
RECOMBINATION EXPERIMENT
TRANSPLANTATION EXPERIMENT
SYNCYTIAL SPECIFICATION
 Characteristic of most insect classes.

 Specification of body regions by interactions between cytoplasmic


regions prior to cellularization of the blastoderm.

 Variable cleavage produces no rigid cell fates for particular nuclei.

 After cellularization, conditional specification is most often seen.


 Cell fates are specified by neighboring cells, & specific amounts of
soluble molecules secreted at a distance from the target cells
(Morphogens).

 Morphogen may specify more than one cell type by forming a


concentration gradient (Morphogen Gradient)

Morphogenic field: group of cells whose position & fate are


specified w.r.t same set of boundaries. General fate of morphogenetic
field is determined & particular field of cells give rise to particular
organ (forelimb, eye, heart, etc.) even when transplanted to a different
 One of the first morphogenetic fields identified was the limb field.

 Prospective forelimb area in tailbud stage of salamander Ambystoma maculatum


shows that center of disc give rise to limb
 Adjacent to it are the cells that will form the
peribrachial flank tissue and the shoulder girdle.
 If all these cells are extirpated from embryo,
limb will still form, somewhat later, from an
additional ring of cells that surrounds this area
(which would not normally form a limb)
 If this last ring of cells is included in the extirpated tissue, no limb will develop.

 Limb Field: larger region cells in the area capable of forming a limb.
DIFFERENTIAL CELL AFFINITY
Thermodynamic Model of Cell Interaction
 Cells interact so as to form an aggregate with the smallest interfacial free energy
i.e. cells rearrange themselves into the most thermodynamically stable pattern.

 If cell types A and B have different strengths of adhesion, and if the strength of A-
A > A-B / B-B connections = sorting will occur, with A cells becoming central.

 If strength of A-A ≤ A-B = aggregate will remain as a random mix of cells.

 If strength of A-A >> >> A-B = A & B cells will form separate aggregates.

 According to this hypothesis: early embryo is existing in an equilibrium state


until some change in gene activity changes the cell surface molecules.

 Movements that result seek to restore the cells to a new equilibrium


Hierarchy of cell sorting in order of

decreasing surface tensions.

The equilibrium configuration reflected the

strength of cell cohesion, with the cell types

having the more cell cohesion segregating

inside the cells with less cohesion.


Cadherins & Cell Adhesion
E-cadherin: epithelial cadherin / uvomorulin /L-CAM: all
early mammalian embryonic cells, even 1-cell stage.
Later, restricted to epithelial tissues of embryos & adults.

P-cadherin (placental cadherin) expressed primarily on


trophoblast cells & on the uterine wall epithelium
N-cadherin (neural cadherin): 1st seen on mesodermal
cells & highly expressed on cells of developing CNS

EP-cadherin (C-cadherin) maintain adhesion between


blastomeres & required for normal movements of
gastrulation

Protocadherins: Ca-dependent adhesion proteins &


differ from classic cadherins in lack of connections to
cytoskeleton through catenins. Protocadherins are very
important in separating notochord from other
mesodermal tissues during gastrulation.
GENOMIC EQUIVALENCE
 Meaning: every cell of an organism indeed had the same set of
genes, or genome, as every other cell.

 Metaplasia / Transdifferentiation: transformation of one


differentiated cell type into another (example of metaplasia)

Synthesis of ribosomes, Differentiation of Continuous mitosis in dorsal


DNA replication & mitosis pigmented iris by throwing iris forming globe of
on dorsal side nuclei of iris out melanocytes which are dedifferentiated cells
digested by macrophages

Differntiated lens forms & These cells starts synthesis


cell division ceases of crystallin protein
Totipotency: Cells capable of directing the entire development of organism

Cell potency is a cell's


ability to differentiate into
other cell types.

Pluoripotency: Stem cell


that has the potential to
differentiate into any of 3
germ layers but not into
extra-embryonic tissues

Multipotency: potential of
progenitor cells to
differentiate into discrete
cell types
oligopotency is the ability of progenitor cells to differentiate into a few cell types
a unipotent cell is the concept that one stem cell has the capacity to differentiate
into only one cell type.

Stem cells: divide to maintain a


self-renewing population and
contribute daughters that will
differentiate.

Cytoplasmic determinants
Induction & competence
Animal containing a gene from other individual (often different species): transgene
are known as transgenic animals

Ian wilmut (1997) cloned Dolly sheep: Somatic


cell nucleus (mammary gland) of female +
Enucleated eggs = Dolly (from donor nuclei)

Polly from same lab = transgenic fetal fibroblast


cells for clotting factor IX
Maintenance of methylation

De novo methyl transferases


Methylation of centromeric repeats

Interact with 3a & 3b to


stimulate methyl transferase

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