development and pattern formation Flashcards
when during embryonic development does patterning occur?
weeks 4-8
what axis do the HOX genes establish?
anterior-posterior
describe the different axes of a hand
anterior = thumb / posterior = little finger
dorsal = back / ventral = front
proximal = arm / distal = fingertips
5 key characteristics of the HOX genes
- temporal and spatial colinearity
- posterior prevalence
- posterior dominance
- redundancy
- colinear expression along the primary embryonic anterior-posterior axis and also regional/organ-specific embryonic axes
temporal and spatial colinearity of the HOX genes
3’ genes are expressed earlier in development and their expression goes more anterior
posterior prevalence
more HOX genes expressed in posterior regions
posterior dominance
if multiple HOX genes have overlapping expression patterns in a certain segment, the protein whose expression ends more posterior will determine the segmental phenotype
phenotype caused by mutation to HOX-D13
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)
what mutation causes synpolydactly?
HOX-D13
how is the anterior-posterior embryonic axis established?
specific spatial and temporal expression patterns of HOX genes
what is the role of the Shh signal transduction pathway in development?
establish a dorsal-ventral axis in the CNS and an anterior-posterior axis in developing limbs
how is the dorsal-ventral axis in the CNS established?
Shh concentration gradient established by Shh-Ptc signalling pathway from organizing center
what are organizing centers?
- notochord (CNS), zone of polarizing activity (developing limb bud)
- secrete Shh during development
describe the concentration gradient of Shh
- greatest closest to notochord => diffuses dorsally and laterall
how does local [Shh] impact CNS development?
Shh diffuses dorsally from notochord to form neural tube:
- high [Shh] => ventral floor plate and motor neurons
- low [Shh] => sensory neurons/ganglia
how does local [Shh] impact somite development?
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)
how does local [Shh] impact limb development?
- 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
Shh signalling pathway
Without Shh, Patched1 inhibits downstream signalling:
- Shh interacts with cell-surface receptor Ptc1
- Negative regulation of pathway by Ptc1 is removed => activation
- Downstream TFs (including GLI3 - repressor) signal
phenotype associated with loss of function Shh mutation
holoprosencephaly
abnormal septation of cerebral hemispheres caused by abnormality in patterning of CNS
phenotype associated with loss of function mutations to Patched (causing constitutive pathway activation)
basal nevus syndrome
skull and rib abnormalities, predisposition to cancer caused by abnormality in skeletal patterning
phenotype associated with GLI3 loss of function
cephalopolysyndactyly or polydactyly
abnormality in patterning of extremities +/- CNS
