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robbypowell's version from 2018-09-27 17:29


Intro Growth & Development:


Question Answer
Growthan increase in size through the formation or enlargement of similar tissues
Developmenta progression of stages taht leads from an undifferentiated state to a highly organized, specialized, and mature state


growth... increase in size of a structure
development... specialization

There are two main means of growth...


-increase in relative number of cells


-increase in the size of cells that make up a structure


so.. you can either grow by cell division or by enlarging the size of a cell

Growth is Differential...

essentially.. differen organ systems grow at different times
e.g. lymphoid growth peaks before puberty then diminishes to adulthood size while cranium has majority of growth much earlier


At the earliest stages of growth... the head grows primarily- the rest of the body lags behind--


90% of neuro and chondrocranial growth completed by 7 years of age


90% of viscerocranial growth completed by 10 years of age
-so what we actually intervene on is about 10% of growth potential


boys have peak growth later than girls and have more growth (as a group)
girls have peak growth earlier than boys and have less growth (as a group) = NIH resource for craniofacial growth


General Embryology:


-prior to implantation


egg is stuck in a meiotic phase which it cannot complete until union with the sperm


egg travels into and through uterine tube...
fertilization typiccaly occurs in the ampulla of the fallopian tube (let's call it a midway point for tube)


union of egg and sperm occurs in three stages corresponding the layers that surround the egg
1- corona radiata


2- zona pellucida
-inly capacitated sperm can pass through this layer... also once a sperm gets through the layer hardens and does not allow others to enter
3- cell membrane of the oocyte


most common ectopic pregnancy = tubal pregnancies (usually in the ampulla)



first week of development

2-4-16 cell stage


Question Answer
16 cell stage is termed the _____Morula


Zona pellucida is still intact until entrance into the uterus
-but why?
-limits growth
-maximized cell contact
-cells differentiate based on location
-periphery = trophoblasts ---> placenta
-inner cells = embryoblast ---> embryo


Day 8-9 already contacted uterine wall
-Trophoblast wears away uterine wall and trophoblasts differentiate
-Embryoblast differentiates into bilaminar disc


-Amniotic cavity is formed between layer of bilaminar disc and lined by amnioblasts
-form large lacunae


Day 11-12
-uteroplacental circulation established

extra-embryonic mesoderm is established by cells of the cytotrophoblast


Day 13
still at point where most energy is spent on embedding into the uterine wall
-hypoblast layer develops yolk sac


Blood supply for embryo
-umbilical artery and vein show around week 2


Question Answer
the embryonic period is from week ___ to week ____week 2-8
The period of greatest susceptibility to teratogens is from week ___ to week ____week 3-8 (embryonic period)
the fetal period is week ___ to week ____week 9-38


key concepts..
-epiblast cells have to migrate-
-prior to this time, these cells are not amenable to migration.
-so they have to transition to a mesenchymal cell, migrate through the primitive steak, and replace the hypoblast layer
-so now we have 3 layers and notochord


-each give off derivatives


-cells migrate to the prechordal and notochordal plate


Neurulation: formation of the early central nervous system... the neural plate grows rapidly... becomes a tube between the ectoderm and notochord
-also forms neural crest from area just lateral to neural plate


so from neurulation, the notochord gets the ectoderm to be induced to form the
-neural tube
-neural crest cells


neural crest cells migrate and give rise to lots of stuff including CNS, PNS, and some important parts of face


Question Answer
cephalocaudal foldingtransition from disc form to fetal position top of the tube overlying the rest of the body
lateral foldingmesoderm (on lateral edge) splits into two and outer edge closes in on itself, enclosing the internal organs
head foldingbrain wraps around top of embryo, overlying primordial mouth and growing close to primodial heart


Question Answer
neural tube disordersspinabifida (there are different presentations)


so that was all we needed for basics of embryology---
Now we go back to facial structures-


Neuaral Crest Cells
-during neurulation, some of the neuroectoderm cells differentiate and are able to migrate... these are true mesenchymal cells


they Migrate
-enter ectoderm
-melanocytes, skin and hair


-through the somites
-sensory ganglia, sympathetic and enteric neurons, Schwann’s cells, cells of the adrenal medulla.
-craniofacial skeleton, neurons of the cranial ganglia, glial cells and melanocytes.


---the migration of these cells divide... and these divisions become different groupings that ARE the pharyngeal arches
branchial arch development around 4-5 weeks
-cardiac bulge is competing for space with these structures


bars of mesenchymal tissue, covered by ectoderm and lined internally with endoderm


development of the lip and palate
Question Answer
-t/f cleft lip and palate is commontrue (on of the most common) the most common 1 in 650 births


embryology of face (week 5-6 completed)
-5 mesenchymal prominences
-mandibular prominences
-maxillary prominences
-frontonasal prominence


-area of invagination (nasal pit) becomes the nose
-pit deepens
-resultant outcroppings (mesial and lateral nasal prominences)
-as maxillary prominences continue to grow, they will meet medial nasal prominence at midline forming upper lip


-nasolacrimal groove --> failure of lateral nasal and maxilla
-become facial cleft


-nose is formed by
-frontal prominence (bridge)
-merged mesial nasal prominences (crest and tip)
-lateral nasal prominences (alae)


one max prom doesn't meet medial nasal ---> lateral cleft lip
both max dont meet medial nasal ---> bilat cleft lip
medial nasal proms fail to meet at midline --> midline cleft lip


median nasal prominences merge to form --
Frontal prominence goes on to form the nasal septum


Secondary palate (max prominence) development --> palate fusion (again from medial nasal prominences and maxillary prominences)
-platal shelves grow from maxillary prominences
-initially grow vertically next to tongue
-embryo tongue is inside nasal cavity


-shelves appear around 6 weeks
-about 7 weeks, shelves achieve a horizontal position above the tongue and fuse creeating the secondary plate
-these shelves fuse with each other and connect to primary palate (premaxilla from medial nasal prominence)


Tongue development (around 4 weeks)


1st arch --> lateral lingual swellings (& medial swelling) --> ant 2/3's of tongue
-lateral lingual swelling becomes ant 2/3's of tongue
3rd arch --> copula --> post 1/3 tongue
4th arch --> epiglottis


what are somites?
-paraxial mesoderm organized into segments based on its position relative to the notochord


-each somite has a nerve associated with it (and are the origins of spinal nerves)


why is this important?
-because occipital somites (of which there are 4 in total) form the bones of the skull


most of the bones of the skull occur from intramembraneous means... but there are some that occur via endochondral




early development of skull
-most cranial base comes from cartilage
-most everything else comes from intramembraneous


the key part about intramembraneous bone formation is that it is vascularized... (endochondral bone formation is not)


intramembraneous formation
-occurs at ossification centers and radiates outward
-lays down osteoid
-is vascular
-happens within collagen membranes


endochondral ossification
-most of the skeleton
-mesenchyme laid down
-primary ossification center
-blood supply comes in for ossification centers
-feeds process through diffusion
-chondrocytes live in the cartilage
-control the expansion of the cartilage
-this is cartilagenous medium is then turned into bone


Mandible develoment
-develops from BOTH Endochondral and Intramembraneous Ossification
-Meckel's Cartilage DOES NOT become the mandible, but is a structure that Intramembraneous bone is built adjacent to
-Meckel's Cartilage does persist as --> Incus, Malleus, Sphenoid spine, Sphenomandibular ligament, genial tubercle
-endochondral development occurs in the condylar and coronoid regions


skull divided into
-brain vault
-facial structures


--mostly the anterior portion of craniofacial is neural crest
-posterior derived from occipital somites


Growth of Intramembraneous neurocranium occurs by apposition outside and resorption inside (allowing for more space for brain)
Growth of cartilagenous neuorcranium
-base of occipital bone (a portion)


so occipital bones are also mixed formation bones (like mandible)
principles of postnatal growth
-90% of chondrocranial growth completed by 7 years of age
-90% of viscerocranial growth completed by age 10


interstitial vs appositional growth
-growth within a bone
-associated with long bone growth
-epiphyseal plates (cartilagenous)
-growh ON existing surfaces
-associated with changes in width or remodeling


so one mechanism of bone growth is Deposition vs resorption
-especially seen in growth of lateral and superior brain growth


-mineral homeostasis


-relocation of synchronous cortical remodeling
-e.g. palatal seems to drift inferiorly if the appository surface is in oral cavity and resorptive side is in nasal cavity


-physical movement of a bone or region due to its own growth
-due to growth of other peripheral structures


-V principle


Theories of Craniofacial Growth
-Sutural (sicher)
-Nasal Septum (Scott)
-Functional Matix (moss)
-Von Limborgh's compromise
-cybernetic theory (petrovic)


Sutural (sicher) (historic thought.. DISPROVEN)
-"sutures are primary determinant of craniofacial growth"
-sutures as growth centers


-What is a suture in reality?
-sites of bone growth (deposition)
-articulations between bones and hold cranium together
-perhaps act as shock absorbers early on
-derived from Ectomeninx


-data suggested that sutures are actually passive responders
-tested by autotransplantations
-don't act as growth centers
-IF you cut sutures out, bone growth doesn't stop (in craniosynostoses)


Scott's Cartilagenous Theory/Nasal Septum (partially true)
-cartilagenous growth centers drive growth
-facial growth driven by nasal septum
-cranial base growth driven by synchondroses cartilage
-there is some data supporting
-cut out nasal septum --> midflace hypoplasia
-identification of the septo-premaxillary ligament...
-**important to A-P growth of maxilla, but not shown to be true otherwise**


Functional Matrix Hypothesis
-"all bone and cartilage growth is controlled by extrinsic (epigenetic) soft tissue matrix growth and muscle function


-functions of the skull region


-each matrix consists of:
-bone component


Skeletal units
Microskeletal unit


2 types of matrices:
-orocapsular matrix
-orbitocapsular matrix




Macrounit = core of bone
microunit = modulated by periosteal matrix


-not quantitative
-does not explain how epigenetic signals are induced


"faces grow spaces" theories


Melvin Johnston (interesting reads)
-trashes Moss's Functional Matrix Theory


Compromise theory these factors contribute (a little bit of all previous thoughts)
-intrinsic genetic
-local epigenetic
-general epigenetic
-local environmental
-general environmental


-2 factors
-hormonally regulated growth of midface and anterior cranial base
-provides constantly constantly changing reference input via the occlusion
-Rate limiting effect of growth of the midface on the growth of the mandible


-growth of face is primarily driven by cranial base and nasal septum under influence of endocrine system


-evidence against theory
-lateral pterygoid transection doesnt affect
-condylar transection doesn't effect later mandibular growth


*** when reading Moss's work... look at his 60's stuff... not his 90's stuff


Post-Natal Growth of Individual Craniofacial Components


dolicho versus brachy growth could have to do with the timing of sutures-
---> this would then, could then affect facial development --> possibilities of malocclusion




our brains are done growing by 7 or 8 years of age... so why do we maintain sutures so long?
-perhaps because they're shock absorbers


"parasagittal suture"




-portions of tongue come from different branchial arches
-ant 2/3's


-post 1/3




important summary ---
day 8 implant
day 12, 13 placental circulation is established & mom's blood can start to affect embryo
-around the same time that


how long does fetal development occur? 38 weeks (embryonic weeks)


continued growth in different dimensions




-down and forward driven by
-displacement of nasomaxillary complex causing apposition at sutures (1/2 of all growth)
-remodeling causing inferior relocation of palate and maxillary arch


-anterior bone deposition until 5-6 years
-Posterior deposition (near maxillary tuberosity) causes anterior displacement
-Amount of forward displacement is matched by posterior bone growth
-Increases in length until the midpalatal suture ceases growth
-The remodeling of the maxilla leads to widening


gonial angle subject to a lot of remodeling affected by pterygomasseteric sling


-mandibular synostosis is a growth center and fuses around 1 year of age
-how could breastfeeding or other oral behaviors affect mandibular symphisis?