BMS1021 PASS - Week 5

● Describe the basic stages of development, Hox genes and Homeobox mutations
● Understand the difference between genetic and teratogen-induced birth defects using
examples
● Describe the basis of Down Syndrome and the effects of thalidomide and alcohol on the
foetus

MCQs
1. What is the name given to the group of transcription factors giving positional information to an
organism during its development?
a. Hox genes
b. Homeobox genes
c. Homeodomains
d. Somites

2. What results from a mutation to a Hox gene?

a. Homeotic transformation
b. Mirror duplication of a limb
c. Fusion of limbs as they are growing out
d. Failure for a limb to grow

3. Which of the following is not a basic stage of development?

a. Gastrulation
b. Limb Growth
c. Morphogenesis
d. Cleavage

4. What results when transplantation of leg bud mesoderm is transferred to the wing bud in
Chick embryos?
a. The wing will become chimeric for wing base but leg tip
b. The limb will fail to grow and the animal will lack a wing here
c. A leg will form where the wing should be
d. The wing will mirror duplicate itself

5. Which of the following does not influence the effect of a teratogen?

a. Developmental stage at time of exposure
b. Genotype of the mother and the foetus
c. Dose and duration
d. Time of the day

6. Which of the following is correct about Down Syndrome?

a. It is due to monosomy 21
b. It is due to non-disjunction during mitosis
c. It leads to the over-expression chromosome 21
d. It does not affect the phenotype

7. Which option correctly matches the teratogen with its effect?

a. Xenoestrogens → 'DES daughters'
b. Thalidomide → Amelia
c. Alcohol → impaired testis function
d. Diethylstilbestrol → FAS

8. During which stage does somitogenesis occur?

 a. Gastrulation
b. Pattern formation
c. Morphogenesis
d. Cell differentiation

9. Which of the following is true about homeobox genes?

a. They exist only in Drosophila melanogaster
b. They lay the pattern for dorsal-ventral segments
c. The genes are expressed in overlapping areas
d. A single cluster of homeobox genes is found in mammals

SA

1. Describe each of the 6 basic stages of development.

a. Cleavage Divisions - egg gets divided into a number of small cells, forming the
morula.
b. Gastrulation - generation of the three primary germ layers.
c. Pattern Formation - establishment of body plan (segmentation, limb bud generation,
etc.)
d. Morphogenesis - change in form.
e. Cell Differentiation - Cells become structurally and functionally different from each
other.
f. Growth - increase in body size.

2. What is the difference between Hox genes, Homeobox genes and Homeodomains? Try
to write a 1- 2 sentence definition of each.
● Homeodomain = in protein
○ Encoded by homeobox
○ Binds DNA where protein functions as transcription factor – gene regulation
● Homeobox = in gene
○ Family of highly conserved developmental control genes
○ Provide positional information to cells during development
○ Dispersed throughout genome but grouped in clusters (hox genes)
● Hox = cluster of homeobox genes
○ Expressed in overlapping domains along the anterior-posterior axis
○ expression domains are co-linear with their position along the chromosome
○ control regional identity of body parts – role in axial patterning
○ major sites of expression – somites, brain and SC, limbs

^ unique combinations of Hox proteins along the body axis specify positional information

3. Describe the process of segmentation by somitogenesis and how each of the somites
adopts its eventual fate?
a. Involves the body’s axis being divided into a repetitive series of similar but
independent developmental units called Somites.
 b. Each somite experiences differential gene expression along the axis. The genes
being differentially expressed in these regions are Hox genes.

4. Explain the co-linear arrangement of Hox genes in mammals? What would happen if a
Hox gene from the thorax region was activated in the head region of Drosophila
melanogaster and what is the name of this condition?
a. Hox gene are arranged linearly along a chromosome in the same way that they are
sequentially activated along the body axis of the embryo.
b. A leg would form on the head of the fly. This is known as Antennpedia.

5. Describe the basis of Downs Syndrome.

● Syndrome = several developmental anomalies co-existing
○ Often due to several genes on the chromosome being affected, or, one gene
having multiple effects when mutated (pleiotropy)
● Downs:
○ Due to trisomy 21 (3 copies of chromosome 21)
○ Non-disjunction during meiosis:
■ Failure of homologous chromosomes to separate at meiosis I, or
■ Failure of sister chromatids to separate at meiosis II
○ Heart, gut anomalies, facial muscle changes — cognitive problems
○ Over-production of proteins from extra chromosome 21
○ Genetic diagnosis by chromosome staining
○ An example of chromosome aneuploidy (error in number)

6. Create a table outlining the difference between genetic and teratogen-induced birth
defects. Provide examples of both types of birth defects.
● Note: birth defect = congenital defect
○ One of their objectives is to “define congenital defect”
● Arise due to developmental anomalies during embryogenesis

Genetic birth defects Teratogen induced birth defects

Description Many birth defects reflect an Many birth defects reflect an interaction of
interaction of genetics environment

Due to a genetic mutation/s Caused by an environmental agent

or change in chromosome number (teratogen)

Inheritance of genetic disorders: Teratogen =

● Single gene disorders can be
dominant, recessive,
autosomal or sex-linked
● Environmental agents that come from
outside the body (usually chemicals)
that cause birth defects
● Interfere with normal development,
enhancing or blocking normal
developmental processes
● Can cross the placenta
● Most sensitive in early embryonic
stages (weeks 3-8) = embryogenesis
and organogenesis occurring

Example Downs Syndrome, achondroplasia, Alcohol, drugs (eg. thalidomide), cigarettes,

cleft palate, spina bifida radiation

7. Describe the effects of thalidomide and alcohol on the foetus.

Thalidomide Alcohol

● An immunomodulatory drug (sedative) ● Alcohol is a very widely used drug in

 first marketed in German in 1957
● Began to be used for nausea and
morning sickness in pregnant women
(first trimester)
● Caused widespread limb deformities in
newborn babies - phocomelia
(malformed limbs) or amelia (no limbs)
● Thalidomide is a teratogen (taken off
market in 1961)
society, and is a teratogen
● Foetal Alcohol Syndrome (FAS): a
cluster of features of babies born to
women who have consumed high levels
of alcohol during pregnancy
● Thought to be most prevalent type of
congenital mental deficiency
● Alcohol effects vary by dose, exposure
time and duration (first 4 weeks critical)
and genetic background
● FAS = difficulty with memory // milder =
problems with planning, decision-making

Mechanism of action as a teratogen; several

hypotheses: ● Petite features, rounded head, thin
upper lip, small nose, low IQ
1. It binds a protein, cereblon, that
interferes with growth signals in early Brain is less-well developed → less neuronal
limb bud connections
2. It blocks blood vessel development in
limb, causing cell death —> limb bud
doesn’t grow

8. Explain DOHaD and provide an example to illustrate this.

● Developmental Origins of Health and Disease (DOHaD)
● Demonstrates link between maternal, perinatal and early childhood factors and the
risk of developing heart disease, diabetes, obesity, cancer and many other non-
communicable diseases (NCDs) in later life
● Certain adult anatomical and physiological features are established at the embryonic
stage, and nutritional deficits at embryonic stage lead to permanent changes that are
reflected in the adult
○ Eg. low birth weight correlates with increased risk of adult disease
○ Eg. famine

EXTENSION

1. Draw a diagram explaining what would happen if you transplanted the organiser cells
into a different embryo in Salamanders.
2. Explain the situation by which a wildtype, heterozygote mutant, and homozygote
mutant mouse for HoxA9 will develop its vertebrae.
● The wildtype will develop normally, with 12 thoracic vertebrae.
● The heterozygous mutant will have a vertebrae after the 12 thoracic vertebrae that
takes on a thoracic appearance with small rib out growths.
● The homozygous mutant will develop a 13th thoracic vertebrae with ribs.