Lecture 7: Developmental Genetics *Due to the unequal distribution of cytoplasmic

environment which triggers differential gene action

Developmental Genetics
- study of the relationships between gene regulation
and cell differentiation during development
Development
- process of regulated growth that results from the
interaction of the genome with the cytoplasm and the
environment
Development involves:
1. Programmed sequence of phenotypic events
typically irreversible
Important to remember:
1. Differential gene function is an intrinsic and
fundamental aspect of cell differentiation
2. Cell phenotype is a consequence of differential
gene action or selective expression of its gene
Points of Control in Eukaryotic Gene Expression
1. Pre – transcriptional
a. Selective DNA replication
- gene amplification

2. Differentiation e.g.: amphibian oocyte

- formation of different cell types, tissues and (rDNA) – rRNA
organs through specific regulation of gene b. Condensation – Decondensation of
expression Chromatin
- Euchromatin (active)
Determination - Heterochromatin (inactive)
- cell makes an irreversible commitment to follow a - DNA Methylation (inactive – highly
certain development path methylated)
2. Transcriptional Control
Determinants a. Differential RNA Synthesis
- cytoplasmic effector substance which cause the cells - Xenopus laevis
to become irreversibly committed to perform a - High rRNA synthesis in immature
specialized function oocytes
- 0 during meiosis or after fertilization
Differentiation - Resumption of rRNA synthesis during
- expression of cells specialized role gastrulation
Specialized Cells b. Differential initiation
- cells producing specialized proteins derived from *two or more TATA box = produce 2 or more types of
luxury genes mRNA
- gene product are not needed for survival
3’------TATA-------TATA---------5’
Ex: 3’------TATA-----------------------5’
Immature RBC – hemoglobin 3’--------------------TATA---------5’
beta cells of pancreas – insulin c. Differentiation polyadenylation (Poly A
Central Question in Developmental Genetics Tail)
- How one cellular genotype gives rise to many *| = poly A
different cellular phenotypes? 3’---TATA--------|-----------|------5’
3’---TATA--------|-------------------5’
Initial Cytoplasmic Environment 3’---TATA---------------------|------5’
- set by maternal genome d. Differential RNA processing
- triggers the switching on of genes - differential splicing
- gene products will occupy a specific position in the egg (introns remove, exons remain)
- when the cell divides, the cytoplasmic environment of
each cell will be different from each other 5’-A--B--C--D--E--F--G--H-3’
5’-A-B-C-D-E-F-G-H-3’
Formation of Different Cellular Phenotypes
5’-A-C-D-E-F-G-H-3’
5’-D-E-F-G-H-3’
 e. Selective pre – mRNA degradation
3. Translational Control
a. Transcriptional Control
ex: sea urchin
- 0 at or before fertilization
- High protein synthesis after fertilization
- Low protein synthesis during
gastrulation
b. Stability of mRNA
- Half-life of mRNA
- Length of the Poly A Tail
- Auto – regulation
e.g.: synthesis of histone
c. Attachment of small residue
- Sialic acid attachment to phosphatase
d. Polymerization
Nucleocytoplasmic Interaction
1. Molecular exchanges between the nucleus and the
cytoplasm
- Experiment done in Amoeba
2. Control of macromolecular synthesis in the
nucleus by the cytoplasm
Genes and Morphogenesis
A. Gene Effects on the system of embryonic
induction
- Organizing tissue of one organ triggers
the development of another organ
- Ureter arises from the mesonephric bud
- Ureter is an organizer in kidney
formation
Effects of Sd
- prevents the normal elongation of mesonephric bud
- ureter which arises from the mesonephric bud must
reach the kidney initial cell
- ureter served as organizer in the formation of the
kidney
B. Gene Effects on Endocrine System
- normal & mutant mice with same rate of
growth initially
- mutant mice stopped growing and never
reached maturity
- absence of large cells in the anterior pituitary
gland
- no secretion of growth hormone
- homozygous recessive
C. Gene Effects on the Regulation of Growth
Metabolism
1. Modifications of a Metabolic process that is
of prime importance to the whole organism
2. Metabolic process is affected => affecting
the characteristics of a particular region =>
change in the growth of the region relative
to the other parts
cpcp – normal
CpCp – lethal
Cpcp – creeper
- Malformations:
- Smaller eyes, no eyelids, misshapen
head, smaller body, skeleton not
ossified
Action of Cp Gene
*Generalized slowing down of growth (36 hr incubation)
=> tissues of hind limb bud (rapidly growing =>
alteration in the development of the embryo
*creeper limbs & smaller body
Gene Effects on Migrating Cells
- genes affect differentiation and migration of cells to
other regions in mice cell; migration is due to w allele
- melanophore migration near embryonic nerve cord
- production of pigments
- RBC migration to the blood forming tissues
- migration of ancestors of germ cells to prospective
genital region
Examples of gene regulation in humans:
*Development of fetus
1st trimester – head fast developing
late part of 1st & 2nd trimester
- limbs develop faster
- development of the trunk
*Development of the nose
- at birth, infants have pug nose
- early child development: nose develops fastest. Large
nose in proportion to the other parts of the face
- after adolescence: nose stop growing, other parts of
the face are growing, 16 to 18 y.o. (proper proportion)
 98 to 99% of DNA of chimps and humans are
identical
 Genes alone don’t dictate the differences
 Depends on molecular switches that tell genes
when and where to turn on and off