Head & Neck Development Flashcards
Genes (DNA) encode (2)
RNA and proteins.
The complement of RNA & protein produced defines the
identity of each cell – its appearance and how it behaves.
Cells receive and process information from their surroundings – (6)
extracellular matrix, secreted molecules (growth factors) from other cells, hormones, contact with other cells (tension), nutrients, oxygen levels, etc.
Cells receive and process information from their surroundings – extracellular matrix, secreted molecules (growth factors) from other cells, hormones, contact with other cells (tension), nutrients, oxygen levels, etc.
•These in turn modify the genes expressed, thus allowing the cell to
adapt to its situation and take on new properties / behaviors
Genes (genome) provide the blueprint that ensures we all have a maxilla and mandible and an integrated oronasal cavity, etc. But gene mutation and differences in these non-genetic ‘instructions’ determines everything about our —.
phenotype
All aspects of the craniofacial complex are defined by
axes: (3)
- Left-right
- Dorsal-ventral
- Anterior-posterior
Clinical treatments always consider: (2)
- form (eg. tooth shape, spacing, number, cusp pattern), and
* symmetry because they are critical for function and esthetics.
Dorsal-ventral axis
•apparent by — stage
blastocyst
Is the D-V axis established as a consequence of cavitation and
formation of inner cell mass (ICM) or is it determined earlier?
Anterior-posterior (A-P) axis [head-tail] and left-
right (L-R) axis determined at start of week 3, with
appearance of the
primitive streak
Epiblastic cells converge at midline and ingress
marks — end
posterior
The Primitive Streak Appearance defines (2) axes
A-P and L-R
Furrow progressively elongates along midline
•through process of
convergent extension
Cells of the epiblast (layer 1) migrate through primitive
streak to form (2)
mesoderm & embryonic (gut) endoderm
•through process of epithelial to mesenchyme transformation (EMT) to form ---
mesoderm
Movement of
epiblast (ectoderm)
to form —- – both
epithelia
embryonic
endoderm
Disproportionate — of the germ layers
growth
Greater proliferation of
epiblast (ectoderm) because it
also generates all (2)
mesoderm
and embryonic endoderm.
Anterior-most end (ventral side) of primitive streak is
unique in both
appearance and function
The — (or Organizer) is a
conserved structure across all
vertebrates
Node
the node is essential for (2)
•patterning and induction of embryonic cells
(mesoderm and embryonic endoderm)
•establishment of the left-right symmetry
Factors secreted by cells of the Node induce
anteriorly migrating mesoderm to form: (2)
- the prechordal plate
* the notochord
the prechordal plate (2)
- most anterior region of mesoderm
* provides the signals for induction of head structures
the notochord (2)
- transient epithelial-like rod structure along the midline.
* provides the signals for induction of the neural plate
The Node induces the
body axis
The Node induces the body axis
> Induce and specify the
fate of the —- as
it is formed
mesoderm
Creation of asymmetry in symmetrical embryo (2)
- First establishes molecular asymmetry
* Conversion into asymmetric organogenesis
Establishing Molecular Asymmetry
Asymmetric expression of morphogenetic factors (eg. SHH, BMP4 & FGF8) around Node > initiates cascade of gene expression to promote asymmetric specialisation / commitment of mesoderm
Nodal cells each have one
motile cilium
A cilium is a membrane covered
extension from the cell that has a microtubule cytoskeleton core which helps define the
properties of the cilium: (2)
- mechanosensory, or
* rotational
Nodal cilia have a rotational beat (for a few hours only)
•generates leftward flow, resulting in
asymmetric distribution of
morphogens / growth factors
Reproducible morphological & functional asymmetries in
nearly all
internal organs.
|»_space; Evolutionarily conserved mechanism in vertebrates
In mice, ~– genes affect L-R asymmetry
27
|»_space; cilia function affected; gene expression around Node changes
Organ asymmetry
1 in — people with situs inversus (normal health)
> cf. partial situs which can be deleterious
8500-10000
Factors from the mesoderm
induce thickening of overlying
ectoderm»_space;
neural plate
Neurulation [Neural Tube Formation] precursor to (2)
brain
spinal cord
Signals from notochord induce a
‘hinge’ point (floor plate) to help
drive —
folding
The morphological difference of the anterior-most region of
the neural tube reflects
unique underlying cellular identities
and thus different inductive cues (secreted factors)
Advanced maturity of anterior end > expanded neural plate
|»_space;
future brain
Closure of neural tube
proceeds
anteriorly
and posteriorly from
mid-region
By end of week —, head & neck
region comprises ~half of
embryo.
3
The — membrane serves as the hinge point during cephalization
oropharyngeal
Embryonic Folding
Folding of whole embryo while
cephalization occurs
Folding of whole embryo while cephalization occurs (2)
•Concomitant with formation of
pharyngeal arches (> face & neck)
•Foregut and hindgut specialization
Neural Crest Cells
a unique population of (pluripotent) stem-like cells
originating at the ‘crest’ of the enclosing neural tube.
•Migrate ‘ventro-laterally’ to populate the ventral side of the embryo
•Differentiate into a wide variety of cell types / tissues
NCC generated by
process of epithelial-mesenchymal
transformation (EMT) that is analogous to that generating the
third germ layer (mesoderm)
CNCC migration drives outgrowth of the primitive tissue
masses that will form much of the
head and neck
Cranial Neural Crest Cells
Unique in — potential (distinct from other
neural crest cells)
developmental
Major contributor to craniofacial structure, and
specifically to
mineralized tissues of the oral region
Rhombomeres & Cranial Patterning
CNCC fate determined prior to departure from neural tube
> ie. they have “positional identities”
Multiple visible constrictions in neural tube (2)
•rhombomeres 1 - 8, the diencephalon and anterior mesencephalon
•define distinct populations of CNCC and their route of migration
into early facial tissue.
Reproducible paths of migration
> defined by —
mesoderm
Directed CNCC Migration experiment: Pharyngeal arches 1, 2 & 3 are populated by NC cells from rhombomeres 2, 4 & 6, respectively. >> If r2 cells transplanted to r4 position,
migration still occurs through arch 2
- but cells differentiate into structures
characteristic of arch 1!
Early molecular patterning (est. during gastrulation)
enables later coordinated tissue —.
morphogenesis
Embryogenesis is a ‘—’ process
not descriptive
generative
Malformation and normal phenotypic variation can result
from: (3)
- single changes in gene sequence
- combinations of ‘normal’ gene variants, or
- changes in the ‘environment’ to which cells respond