The document discusses cell lineage studies, tracing the developmental history of cells from precursors to differentiated states, with significant contributions from researchers like Dr. Sydney Brenner, who mapped cell lineage in C. elegans. It highlights the role of genetic and epigenetic factors in determining cell fate, including specific signaling pathways and environmental influences, particularly in plant and mammalian development. Furthermore, it addresses how alterations, such as those caused by prenatal ethanol exposure, can impact cell fate and development across generations.

1. CELL FATE AND LINEAGES
M.SC botany

2. o Cell lineage studies aim to define the developmental history of a
particular cell type from its precursors through their fully
differentiated state.
o The first cell lineage studies were performed by Whitman at the
end of the nineteenth century and consisted of the direct
observation of cleavage patterns in leech embryos.
Cell lineage

3. Since then, multiple techniques have been developed to follow
the fate of cells, including injections of vital dyes or radioactive
molecules in cells of different organisms, introduction of reporter
genes by transfection or viral infection, and transplantation of
embryonic cells and tissues.
More recently, generation of genetically modified mice expressing
reporter genes or Cre recombinase have provided major
advantages for tracing different cell lineages.
Cre recombinase is a site-specific recognition enzyme that
recognizes 34 base-pair LoxP sequences and, depending on
their orientation, excises or inverts the DNA flanked by them.

4. Cre recombinase DNA

5. It was found that in some animal groups, such as nematodes and ascidians, the
pattern of cell divisions was almost identical from individual to individual.
Such ‘invariant’ cell lineages allowed the reconstruction of extensive lineage
trees.
In other animals, such as leeches and insects, stereotyped patterns of cell
division (‘sublineages’) were seen in the progeny of particular precursor cells.
Because of the correlation between cell lineage and cell fate in such invariant
lineages, it was assumed that cell fates were determined by factors segregating
within the dividing cells (termed ‘determinate’ cleavage).
Cell lineage is defined as the pattern of cell divisions in the development of an
organism, whether invariant or not.

6. Cell lineage is the framework for understanding cellular diversity, stability of differentiation, and
its relationship to pluripotency.
C. elegans: model organism
As one of the first pioneers of cell lineage, in the 1960s Dr. Sydney Brenner first began observing
cell differentiation and succession in the nematode Caenorhabditis elegans.
Dr. Brenner chose this organism due to its transparent body, quick reproduction, ease of access,
and small size which made it ideal for following cell lineage under a microscope.
By 1976, Dr. Brenner and his associate, Dr. John Sulston, had identified part of the cell lineage in
the developing nervous system of C. elegans. Recurring results showed that the nematode
was eutelic (each individual experiences the same differentiation pathways).
This research led to the initial observations of programmed cell death, or apoptosis.

8. After mapping various sections of the C.
elegans' cell lineage, Dr. Brenner and his
associates were able to piece together the
first complete and reproducible fate map of
cell lineage.
They later received the 2002 Nobel prize for
their work in genetic regulation of organ
development and programmed cell death.

9. Cell fate is specified by signaling pathways such as the nodal,
fibroblast growth factor (fgf), and bone morphogenetic protein
(bmp) families during the late blastula stage.
Stem cell fate is determined by intrinsic regulators and extrinsic
signals. The physiological environment provides a perfect but
complex combination of signaling, including the appropriate
identity, abundance, location, and dynamics of stimuli that function
in synergy with the intrinsic regulatory network to orchestrate the
temporal-spatial control of self-renewal and differentiation.
CELL FATE

10. DIVERSE CLASS OF CELL FATE

11. CELL FATE IN PLANT
MERISTEM

12.  The shoot apical meristem is initiated during embryogenesis and, after germination of the seed, it
produces the stem, a succession of leaves and flowers.
 The meristems of Arabidopsis are organized into an outer tunica, consisting of two cell layers (L1
and L2), and an inner corpus (L3), which all contribute to organ formation and growth
 Cell divisions within the L1 and L2 are perpendicular to the surface of the meristem (anticlinal), so
that progeny cells will remain in their layer of origin and establish a clone.
 The cells within one clone can have diverse fates: e.g., a stem cell in the L2 can produce daughter
cells that eventually differentiate as subepidermal cells, or even as gametes.
 Both leaves and flowers originate on the flanks of the meristem from the peripheral zone that
surrounds the central zone, where the stem cells reside

13. Cell Fate in Mammalian Development
1) Cell fate commitment is achieved by the establishment of epigenetic
mechanisms.
Epigenetic mechanisms -
Epigenetic mechanisms regulate gene expression at the transcription level by
modulating the accessibility of gene promoter regions to transcriptional
machinery.

14. o Epigenetic mechanisms of gene expression can be influenced by the
environment.
o One such well-established environmental factor that is known to
influence epigenetic mechanisms of gene expression is an
individual’s nutrition.
o An individual’s nutrition is comprised of water, metabolic fuels (mainly
carbohydrates and lipids), proteins, minerals, vitamins, and essential fatty
acids.
Nutritional Effects on Epigenetics

16. Epigenetics of Plants
Plants use epigenetic mechanisms during development and also
across successive generations of whole plants.
DNA methylation, modification of histones, and small RNAs are used
as epigenetic mechanisms, as in most animals.
For example, in some flowering plants, differences in the shape of the
flower or color of the fruit are stable across generations and are due to
inherited differences in the level of promoter methylation.
Methylation of DNA in plants controls such developmental
characteristics as in the ripening of fruits.

17. METHYLATED HISTONE OCTAMER
HISTONE OCTAMER

18. Methylation Controls Ripening of Fruit
When their promoters are methylated, genes involved in plant ripening are
silenced. During development, methyl groups are removed which allows the
transcription factor RIN to bind to the promoters. This allows gene expression
and the fruit will ripen.

19. 2) While the fertilized egg and very earliest blastomeres are
totipotent, progressive stages of embryonic development lead to
restrictions in cell fates and developmental potential.
3) As development proceeds germ cell precursors become
reprogrammed, and thereafter become specialized as they
differentiate into sex-specific gametes exhibiting
specialized epigenomes.
Epigenome means genome-wide epigenetic regulations, including DNA methylation,
post-translational modification of histone, chromatin remodeling, higher-order DNA
organization, and noncoding RNA alterations, all of which are heritable and sequence-
independent.

20. stages of embryonic
development

21. The epigenome of male and female gametes at the time of syngamy is a
product of a long, complex reprogramming process starting with the
naïve epigenome of the primordial germ cells (PGCs).
Epigenomes are sensitive to environmentally induced alterations in gene
expression. These epigenetic modifications can result in reproductive,
behavioral, and metabolic disorders.
Apart from the direct effect on individual epigenomes, the alteration in
the germline can transmit the disorders through generations.

22. Stem cell fate is determined by intrinsic regulators and extrinsic
signals.
The physiological environment provides a perfect but complex
combination of signaling, including the appropriate identity,
abundance, location, and dynamics of stimuli that function in synergy
with the intrinsic regulatory network to orchestrate the temporal-spatial
control of self-renewal and differentiation.
CONTROL OF CELL FATE
4) Erasure of these gamete-specific features is then necessary to enable acquisition
of a totipotent state in the zygote.

23. Some in vivo data support the notion that cell fate can be altered by
ethanol exposure.
Prenatal exposure to ethanol alters the fates of hematopoietic
progenitors in the bone marrow of mouse neonates, and lymphocyte
development is delayed.
Ethanol can affect the differentiation of cycling and recently postmitotic
cells via targeted alterations of genetic expression.