development and pattern formation

Question 1

when during embryonic development does patterning occur?

Answer 1

weeks 4-8

Question 2

what axis do the HOX genes establish?

Answer 2

anterior-posterior

Question 3

describe the different axes of a hand

Answer 3

anterior = thumb / posterior = little finger

dorsal = back / ventral = front

proximal = arm / distal = fingertips

Question 4

5 key characteristics of the HOX genes

Answer 4

1. temporal and spatial colinearity
2. posterior prevalence
3. posterior dominance
4. redundancy
5. colinear expression along the primary embryonic anterior-posterior axis and also regional/organ-specific embryonic axes

Question 5

temporal and spatial colinearity of the HOX genes

Answer 5

3’ genes are expressed earlier in development and their expression goes more anterior

Question 6

posterior prevalence

Answer 6

more HOX genes expressed in posterior regions

Question 7

posterior dominance

Answer 7

if multiple HOX genes have overlapping expression patterns in a certain segment, the protein whose expression ends more posterior will determine the segmental phenotype

Question 8

phenotype caused by mutation to HOX-D13

Answer 8

synpolydactyly

abnormality in segmental identity along the proximal-distal axis of the hand/foot

more distal (metacarpal) bones take on a more proximal phenotype (carpal bones)

Question 9

what mutation causes synpolydactly?

Answer 9

HOX-D13

Question 10

how is the anterior-posterior embryonic axis established?

Answer 10

specific spatial and temporal expression patterns of HOX genes

Question 11

what is the role of the Shh signal transduction pathway in development?

Answer 11

establish a dorsal-ventral axis in the CNS and an anterior-posterior axis in developing limbs

Question 12

how is the dorsal-ventral axis in the CNS established?

Answer 12

Shh concentration gradient established by Shh-Ptc signalling pathway from organizing center

Question 13

what are organizing centers?

Answer 13

• notochord (CNS), zone of polarizing activity (developing limb bud)
• secrete Shh during development

Question 14

describe the concentration gradient of Shh

Answer 14

• greatest closest to notochord => diffuses dorsally and laterall

Question 15

how does local [Shh] impact CNS development?

Answer 15

Shh diffuses dorsally from notochord to form neural tube:

• high [Shh] => ventral floor plate and motor neurons
• low [Shh] => sensory neurons/ganglia

Question 16

how does local [Shh] impact somite development?

Answer 16

Shh diffuses laterally from notochord to affect somites.

• high [Shh] = ventral-medial somite => sclerotome (vertebral body/rib precursor)
• low [Shh] = dorsal-lateral somite => dermomyotome (dermis and musculature precursor)

Question 17

how does local [Shh] impact limb development?

Answer 17

• Shh secreted from zone of polarizing activity in the proximal-posterior aspect of the limb bud
• concentration gradient with high [Shh] at little finger side and low [Shh] at thumb side

=> defines anterior-posterior axis

Question 18

Shh signalling pathway

Answer 18

Without Shh, Patched1 inhibits downstream signalling:

1. Shh interacts with cell-surface receptor Ptc1
2. Negative regulation of pathway by Ptc1 is removed => activation
3. Downstream TFs (including GLI3 - repressor) signal

Question 19

phenotype associated with loss of function Shh mutation

Answer 19

holoprosencephaly

abnormal septation of cerebral hemispheres caused by abnormality in patterning of CNS

Question 20

phenotype associated with loss of function mutations to Patched (causing constitutive pathway activation)

Answer 20

basal nevus syndrome

skull and rib abnormalities, predisposition to cancer caused by abnormality in skeletal patterning

Question 21

phenotype associated with GLI3 loss of function

Answer 21

cephalopolysyndactyly or polydactyly

abnormality in patterning of extremities +/- CNS