L5 Human Developmental Genetics 2

Question 1

Primitive streak drives the body plan

Answer 1

see one note slides

defines the body axes and determines further elaboration of body plant

is an organiser

Question 2

Neurulation

Answer 2

see onenote slides

the formation of the neural tube

after gastrulation

region of the ectoderm thickens into the neural plate, this tissue then undergoes epithelial folding to eventually form the neural tube

Neural crest cells undergo EMT and migrate out

Question 3

Neural tube defects (NTDs)

Answer 3

affect 1 in every 1000 pregnancies

anencephaly - failure to close the anterior neuropore

spina bifida - failure to close the posterior neuropore

genetics behind neural tube closure is complex

Question 4

Formation of neural crest cells

Answer 4

see onenote

in region between neural plate and epidermis, distinct type of cell is specified. They undergo EMT and begin to migrate throughout the body

EMT dependent on Snail family gene SLUG (Snail 2)

Question 5

The neural crest - “the fourth germ layer”

Answer 5

see onenote

move throughout the body and differentiate into many types of cells

Neural crest cell

• Go into the growing embryonic body and creates the tissues we need e.g. melanocytes
• Specific to vertebrates

Question 6

Waardenburg’s syndrome and the neural crest

Answer 6

see onenote slides

mapped the causative dominant mutation to the short arm of chromosome 3

MITF gene - mouse model

due to failure in formation/migration of melanocytes

• white forelock due to failure of melanocytes to migrate out to the tip of the developing forehead
• the deafness is because melanocytes help form part of the inner ear

Question 7

Making neurons and glia

Answer 7

see onenote

neuroepithelial cells are called neural stem cells

Question 8

Generating diversity by asymmetric divisions

Answer 8

see onenote

orientation of division plane determines what sort of division

Question 9

The neural tube is patterned by signalling gradients

Answer 9

see onenote slides

patterned by opposing gradients of sonic hedgehog (Shh) and BMP4

neurons differentiate into different types depending on local level of Shh and BMP

Shh expressed in notochord and floor plate

BMP4 expressed in epidermis and roof plate

Question 10

Holoprosencephaly (HPE)

Answer 10

most common structural anomaly of the developing forebrain, results from incomplete cleavage of the forebrain

severity can range from cyclopia with a single eye and proboscis forming, to a midline facial clefts or in the mildest cases, a single central incisor

occurs quite frequently

Question 11

Shh pathway plays central role in specifying ventral midline

Answer 11

see onenote

Shh expressed in ventral midline

• represses expression of genes such as Pax6 that specify lateral cell fates
• in absence of Shh, brain hemispheres don’t separate and genes such as Pax6 are expressed in the central area only

Question 12

Shh pathway necessary to separate the brain hemispheres

Answer 12

see onenote

Shh not activated => structures that normally develop bilaterally e.g. the eye filed and nostrils fail to separate

Question 13

Segmentation in vertebrates

Answer 13

see onenote

DLL3 (delta like 3) is a ligand that activates the notch pathway

Question 14

Segmentation begins with somites

Answer 14

see onenote

Somites are bilaterally paired blocks of paraxial mesoderm that form along the head-to-tail axis of the developing embryo in segmented animals.

Question 15

Somitogenesis involves MET

Answer 15

see onenote

somites form from mesodermal cells (called presomitic mesoderm) which self-organise into an epithelium

undergo MET

Question 16

Somite formation involves a genetic clock

Answer 16

see onenote slides

Question 17

clock and wavefront

Answer 17

see onenote slides

cells which are anterior to the wavefront and have notch activation become determined to differentiate into somites

Question 18

Congenital mirror movements disorder

Answer 18

see onenote

Mutations in DCC cause congenial mirror movements

Question 19

DCC is a receptor for the diffusable axonal chemoattractant Netrin-1

Answer 19

see onenote slides

DCC = deleted in colorectal carcinoma

DCC binds to netrin

Netrin secreted through the neural tube - guidance molecule

Axon activated by netrin and neurons will move towards the netrin source if the axon expresses the DCC receptor

Without netrin/DCC, guidance across midline does not occur => no axon crossing over the midline

Question 20

Hypothetical model for mirror movements

Answer 20

see onenote slides