Chapter 5 - Genetics and the Development of the Human Brain

Question 1

GENOTYPE

Answer 1

The genetic composition of an organism - it consists of 23 matched pairs of chromosomes, which are made up of DNA molecules.

Question 2

PHENOTYPE

Answer 2

The observable appearance of an organism produced by the interaction between environmental influences and its genotype.

Question 3

GENES

Answer 3

Genes are small segments of DNA. constructed from combination of four organic basis: ADENINE, THYMINE, GUANINE and CYTOSINE,

Question 4

TRANSCRIPTION

Answer 4

It takes place in the nucleus, where an enzyme called RNA polymerase attaches to the start of a gene and produces a mold of the gene on a strand of RNA, using URACIL instead of THYMINE.

Question 5

TRANSLATION

Answer 5

In the cytoplasm, RIBOSOMES read and interpret the CODONS of the RNA strand, providing amminacids which, joined together, form proteins.

Question 6

ALLELES

Answer 6

Alternative versions of a particular genes. If a person has two identical alleles, the individual is considered to be HOMOZYGOUS for that gene. If a person has two different alleles, they are HETEROZYGOUS for that gene.
A RECESSIVE allele will produce its phenotype only when it occurs in a homozygous pair, whereas a DOMINANT allele will produce its phenotype in any case.

Question 7

SOURCES of GENETIC VARIABILITY

Answer 7

Genetic variability is produced by several processes.
1) CROSSING OVER:
Egg and sperm cells are formed through the process of MEIOSIS, in which parental chromosome pairs are divided in half, leav­ing only one chromosome from each pair in an egg or sperm cell. In the process of CROSSING OVER, chromosomes lining up prior to meiotic division physically cross one another and exchange equivalent sections of genetic material. This results in unique combinations of alleles not seen in either parent.

2) MUTATIONS:
During chromosome replication, MUTATIONS happen, yet the vast majority of it has no effect. There are three types of mutation, namely SUBSTITUTION, INSERTION, and DELETION.

3) SEX CHROMOSOMES:
sex chromosomes feature different sets of genes with only a small number of overlaps. Therefore, males are more likely to have sex-linked disorders, as a single recessive gene in X will be expressed. In females, the process of X CHROMOSOME INACTIVATION randomly silences most of the genes of one X chromosome. Which X chromosomes is silenced varies from cell to cell - for this reason, only female cats can be calicos because the alleles for orange or black fur are located at the same location on the X chromosome.

Question 8

HERITABILITY

Answer 8

HERITABILITY describes how much variation in a trait observed in a population is due to genetic differences.

Question 9

EPIGENETICS

Answer 9

EPIGENETICS refers to the development of potentially herita­ble traits due to changes in gene expression that do not involve changes in DNA sequences - phenotype can change without a corresponding change in genotype.
Modification leading to differences in gene expression are known as EPIGENETIC TAGS - epigenetic tags influence behaviour, but behaviour also affects epigenetic tags. Modifications occur on HISTONES, proteins around which DNA is tightly wrapped.

Question 10

ZYGOTE, EMBRYO and FETUS

Answer 10

The initial cell formed by the merger of egg and sperm is known as a ZYGOTE.
From gestational week 2 to 8, the developing individual is known as an EMBRYO.
After gestational week 8 until birth, the individual is a FETUS.

Question 11

GERM LAYERS

Answer 11

At the end of gestational week one the human zygote has already formed three differentiated bands of cells known as germ layers:

1) the ECTODERM, the outer layer, which will develop into the nervous system, hair and skin;
2) the MESODERM, the middle layer, which will develop into connective tissue, muscles, blood vessels, bone, and the urogenital systems;
3) the ENDODERM, the inner layer, which will develop into many of the internal organs.

Question 12

NEURAL PLATE and NEURAL TUBE

Answer 12

During gestational week three, cells in the ectoderm begin to differentiate into a new layer known as the NEURAL PLATE. Soon after, a depression forms along the midline of the neural tube and to ridges on each side develop to form the NEURAL TUBE. The neural tube will be retained in the adult brain as the system of ventricles, whereas the surrounding tissue will form the brain and the spinal cord.

At the end of gestational week four, the neural tube features three bulges:

1) the PROSENCEPHALON - future forebrain;
2) the MESENCEPHALON - future midbrain;
3) the RHOMBENCEPHALON - future hindbrain.

Further differentiations take place:

1) the prosencephalon divides in DIENCEPHALON and TELENCEPHALON;
2) the rhombencephalon divides in MYELENCEPHALON and METENCEPHALON.

Question 13

6 STAGES OF NEURAL DEVELOPMENT

Answer 13

The development of the nervous system proceeds in a series of six distinct stages:

1) NEUROGENESIS, or the continued birth of neurons and glia;
2) MIGRATION of cells to their eventual locations in the nervous system;
3) DIFFERENTIATION of neurons into dis­tinctive types;
4) formation of connections between neurons - growth of AXONS, DENDRITES and SYNAPSES;
5) DEATH of particular neurons;
6) rearrangement of neural connections - PRUNING and MYELINATION.

Question 14

1 - NEUROGENESIS

Answer 14

NEUROGENESIS - the birth of new neurons and glia - occurs in the ventricular zone in the inner face of the neural tube.
At first, cells duplicate by MITOSIS along lines that are PERPENDICULAR to the surface of the ventricular zone producing additional progenitor cells.
Then some daughter cells divide along lines that are PARALLEL to the ventricular zone, forming cells that will migrate away.
At this stage as many as 250000 new cells per minute are produced - until the 4th month of gestation.

Question 15

2 - CELL MIGRATION

Answer 15

CELL MIGRATION is guided by RADIAL GLIA, progenitor cells that grow out from the ventricular layer to the outer surface of the nervous system.
2/3 of migrating cells wrap around the radial glia and move along them;
1/3 of new cells migrate horizontally - with no need for radial glia.
Migrating cells form the cerebral cortex in an INSIDE-OUT FASHION - cells destined for the outer cortical layers must travel through the inner layers. Once migration is complete, most - but not all - radial glia pull back their branches.

Question 16

3 - DIFFERENTIATION OF CELLS

Answer 16

Stem cells go through DIFFERENTIATION - the development of more specialized cell types from stem cells.
There are two types of differentiation:
1) along the DORSAL-VENTRAL AXIS, neurons in the ventral half develop into MOTOR neurons, whereas neurons in the dorsal half develop into SENSORY neurons.
2) along the ROSTRAL-CAUDAL AXIS, neurons differentiation results in in the division of the nervous system into the spinal cord, hind­brain, midbrain, and forebrain. The differentiation of the SPINAL CORD and HINDBRAIN is guided by proteins encoded by HOX genes - this does not happen for the forebrain and midbrain.

Question 17

4A - GROWTH of AXONS and DENDRITES

Answer 17

Developing axons and dendrites end in GROWTH CONES, which both sensory and motor abilities and have three structural components:

1) a main BODY containing mitochondria and microtubules;
2) FILOPODIA, spiky extensions;
3) LAMELLIPODIA, fan-shaped extensions located between the filopodia.

Both filopodia and lamellipodia have motor abilities and interact with the extracellular environment, guiding the fiber nerve - they can stick to specific cells pulling the growing axon or dendrite behind them. MICROTUBULES from the main body move forward forming a new segment of the axon/dendrite.

The FILOPODIA respond to both attracting and inhibiting chemicals released by GUIDEPOST CELLS along the way, which attract or repel an approaching growth cone.

Growth cones can also attach to other axons travelling in the same direction in a process known as FASCICULATION.

Question 18

4B - FORMATION OF SYNAPSES - SYNAPTOGENESIS

Answer 18

SYNAPTOGENESIS from birth to about the age of four years is double that seen in adults. This growth rate is maintained until 10 years of age, at which times it declines to reach adult levels at 17 years of age.
Synaptogenesis is easily observed at the neuromuscular junction:
1) Initially, ACh receptors are evenly distributed within the membrane of the muscle fiber;
2) Then, chemical releases by both presynaptic and postsynaptic structures stimulate movements of receptors to the synaptic site;
3) Once the synapse is mature the receptors are densely clustered at synaptic sites and rarely found in nonsynaptic areas.

Synaptogenesis is aided by chemicals released by ASTROCYTES.

Question 19

5 - PROGRAMMED CELL DEATH - APOPTOSIS

Answer 19

Following migration, as many as 40 to 75 percent of cells die in a process known as APOPTOSIS, or programmed cell death.
NEUROTROPHINS - chemicals released by target cells and absorbed by developing neurons - promote the survival of a neuron by interrupting cellular sui­cide programs. All cells contain cell death genes which activate enzymes known as CASPASES, which in turn break down DNA and protein and produce apoptosis. In the presence of neurotrophins, caspases production is inhibited.
Apoptosis is an then ACTIVE PROCESS that must be inhibited by neurotrophins.

Higher than normal concentrations of neurotrophins (hence lower apoptosis rates) characterize ASD.

Question 20

6A - SYNAPTIC PRUNING

Answer 20

Not only we lose neurons during development, but also synapses, in a process known as SYNAPTIC PRUNING. Only those synapses that participate in functional neural networks are maintained - according to a “use it or lose it” philosophy.
We initially have a burst of synaptic growth which peaks at 8 months, but then there is a reduction of non-functional synapses.

Question 21

6B - MYELINATION

Answer 21

MYELINATION - the formation of myelin sheaths on certain axons - begins at the sixth gestational month and proliferates around the time of birth. It follows two patterns:

1) it occurs in a rostral direction starting with the spinal cord, then hindbrain, midbrain and forebrain;
2) sensory areas of the cortex are myelinated before motor areas.

The prefron­tal cortex - responsible for higher-order cognitive functions - is not completely myelinated until early adulthood

Question 22

EFFECTS of EXPERIENCE on DEVELOPMENT

Answer 22

Experience in psychobiology results in change of the strength of synapses - in some cases, the time frame of this plasticity is limited and is referred to as CRITICAL PERIOD. Critical periods of development are evident in:
1) the development of the VISUAL SYSTEM:
- in a study on kittens, the right eye was sutured closed for the first three months of life. Then the right eye was opened, and the left eye was sutured closed for the next three months. Most neurons in the visual cortex responded mainly to info captured by the left eye, which had been opened during the critical period of vision development.
2) the development of SOCIAL BEHAVIOUR:
- children in Romanian orphanages in the 1970s who had few social stimuli - they could not interact with others - provide insight on
the critical period of social behavior development. Maladjusted children adopted prior to six months of age appear to have recovered from their earlier deprivation, whereas children adopted later in life improved but did not make as good a recovery as the children adopted earlier.

Question 23

3 types of DISORDERS of NERVOUS SYSTEM DEVELOPMENT

Answer 23

There are 3 different types of disorders that might occur during development:

1) NEURAL TUBE DEFECTS;
2) GENETIC DISORDERS;
3) disorders caused by ENVIRONMENTAL TOXINS - FETAL ALCOHOL SYNDROME

Question 24

1 - NEURAL TUBE DEFECTS

Answer 24

Two major types of neural tube defects are:

1) ANENCEPHALY, in which significant portions of the brain and skull fail to develop, occurs when the ROSTRAL neural tube does not develop properly. The majority of fetuses with anencephaly either die in utero or do not survive for more than a few hours after birth.
2) SPINA BIFIDA, in which the the CAUDAL portion of the neural tube fails to close normally, might result in paralysis and spine and limb deformities. Surgery within the first 24 hours of life is critical for the survival of the newborn. Deficiencies of FOLICIC ACID might be responsible for a large number of cases.

Question 25

2 - GENETIC DISORDERS

Answer 25

Three of the most common genetic disorders are:

a) DOWN SYNDROME;
b) FRAGILE X SYNDROME;
c) PHENYLKETONURIA (PKU).

Question 26

DOWN SYNDROME

Answer 26

DOWN SYNDROME - also known as TRISOMY 21 - is a genetic disorder characterised by an extra copy of CHROMOSOME 21. The major cause of trisomy 21 is abnormal division of the MOTHER’s 21st chromosome during the final meiosis that results in a mature ovum or egg. Down syndrome occurs about once out of 1000 births and the chances of having a child with down syndrome are positively correlated with the mother’s age. Individuals with Down syndrome usually function in the moderate range of intellectual disability.
Phenotypical traits of Down syndrome include a small skull, large tongue, almond-shaped eyes, a flat nasal bridge, and deformities of hands, fingers and heart.

Question 27

FRAGILE X SYNDROME

Answer 27

FRAGILE X SYNDROME is a sex-linked genetic disorder . The FMR-1 GENE - located on the X chromosome - typically has between 6 and 50 codon repeats - consecutive segments of the same codon. Having more than 200 repeats leads to the fragile-X condition, which results in typical intelligence to moderate intellectual disability. Phenotypical traits of the disorder include a large forehead and low-set ears.

Question 28

PHENYLKETONURIA (PKU)

Answer 28

PHENYLKETONURIA is a genetic disorder characterised by having a recessive gene on CHROMOSOME 12 that leads to a lack of enzymes needed to convert the amino acid PHENYLALANINE into tyrosine. People with PKU produce an abnormal byproduct which damages the brain in early development. Intellectual disability - the main effect of the disorder - can be prevented by avoiding foods containing phenylalanine until a person’s mid-20s.

Question 29

3 - disorders caused by ENVIRONMENTAL TOXINS - FETAL ALCOHOL SYNDROME

Answer 29

Maternal alcohol use - which leads to FETAL ALCOHOL SYNDROME - is the most thoroughly understood environmental cause of disorders in the development of the nervous system. Alcohol can freely enter the fetus’ blood supply, where it is not processed in the same way as it is in an adult brain. Alcohol in the fetus prevents necessary nutrition and oxygenation , which affect CELL MIGRATION. FAS children experience growth retar­dation, skin folds at the corners of the eyes, nose and mouth abnormalities, small head circumference, reduced IQ, attention deficits and poor impulse control.

Question 30

the BRAIN ACROSS the LIFESPAN

Answer 30

• from gestation to 3 years of age, the majority of human brain development takes place;
• at puberty, a second wave of gray matter development takes place, resulting in thickening of the cortex - especially in the frontal lobes. A gradual thinning - caused by pruning - follows.
• at 25 years of age, the brain is fully mature.
• at 45 years of age, the weight of the brain begins to decrease, even though ADULT NEUROGENESIS takes place.

The numbers of neurons added to the mature brain are quite small compared to those of neurogenesis early in development. Nevertheless, ADULT NEUROGENESIS may play a role in adult learning and memory, and they might protect the mature brain from the effects of stress.

Question 31

ALZHEIMER’S DISEASE

Answer 31

ALZHEIMER’S DISEASE is a neurodegenerative disorder that typically affects individuals after the age of 70. Its behavioral features include memory loss, delusional thinking, poorer language, problem-solving and social skills.
In individuals affected by the disease, AMYLOID proteins accumulate, disrupting MICROTUBULES by detaching TAU proteins from their surface. TAU protein accumulate in NEUROFIBRILLARY TANGLES, which cause cell death, whereas AMYLOID proteins accumulate in SENILE PLAQUES.