Transcript BIOL 112 – Principles of Zoology

Developmental Genetics,
I.
II.
III.
How do different cell types become organized
into tissues, organs & systems?
Sex determination in Drosophila
Sex determination in Mammals
Genetics of development
zygote
adult
The transformation from a zygote to a
multicelled organism involves a series
of “genetic switches” that regulate a
cascade of developmental events
Developmental Genetics:
Subfield of genetics concerned with the roles genes play in
orchestrating the changes that occur during development.
model organisms: fruit fly, nematode, frog, mouse
Differential cell types of the body are
distinguished by the variety and
amounts of protein that they express
Genetic regulatory decisions:
 what
 where
 when
 how much
I. How do different cell types become
organized into tissues, organs & systems?
A. Developmental pathway:


1.
2.
Developmental pathways consist of sequences
of various regulatory steps
In development, cells commit to specific fates
and differentially express subsets of genes
Determination
Differentiation
B. Major decisions controlled at the
gene transcription level:
→
→
→
→
Separation of the germ line
Establishment of the sex
Establishment of positional information
Subdivision of the body into segments
(anterior-posterior)
→ Subdivision into germ layers (dorsalventral)
II. Sex Determination in
Drosophila
 1993 Nobel Prize - Every cell
determines its sex independently
 each cell lineage makes sexual
decision
 Ratio of X chromosomes to
Autosomes is what determines
sex, creating a cascade of
differential (alternate) mRNA
splicing
 If the pre-mRNA is spliced one
way = female, if spliced another
= male
sex determined by ratio of
X chromosomes to
autosomes (A)
XY, AA and XO, AA –
X:A ratio of 0.5, male
XX AA and XXX AAA –
X:A ratio of 1.0, female
Sxl gene and downstream genes tra and dsx
determine sex
Sxl “off” produces males
Sxl “on” produces females

Ratio of X-chromosome transcription factors (NUM) to
autosomal transcription factors (DEM) affect transcription of
Sxl
basic helix-loop-helix transcription factors (bHLH)
function as dimers
SXL protein activates downstream pathway that leads to
female development
Maintaining the switch
1. Early promotor of Sxl is activated early in embryogenesis.
2. Later, and for the rest of the life, Sxl is transcribed from the late
promoter
 Late Sxl transcript is longer, and subject to alternative
splicing
In the presence of SXL a feedback loop is set up maintaining
SXL activity:
a) SXL causes Female-specific splicing of tra that leads to
active TRA
b) TRA causes female splicing of dsx…
c) DSX inactivates male specific genes leading to female
development
In absence of SXL, there is no functional TRA protein, and dsx
is spliced to produce DSX-M transcription factor which
represses female-specific genes, leading to male development
Sex determination pathway is constructed so that the
activities of several gene products are needed to shunt
the animal from the default state into the female
developmental pathway
III. Sex determination in mammals
 Not independent for each cell
 SRY region on Y chromosome codes for TDF which
determines maleness (binds to DNA and regulates genes
controlling the development of the testis)
 endocrine hormonal system
 Sex is determined by the presence or absence of the Y
chromosome
• Primordial germ cells migrate to the genital ridge,
presence of Y determines if they will organize into
testes….
• Testosterone will be produced, and this hormone binds to
androgen receptors which function as transcription factors
• In XX individuals, absence of SRY and subsequent
absence of testosterone results in default female shunt
pathway
TDF found on the Y chromosome, causes the male pathway
to be activated. This encodes a transcription factor SRY…
Transcription Factors
Repressor
Dosage compensation in Humans,
different than Drosophila