Exam 2 Flashcards
Zones of the mesoderm
Paraxial: thick column of mesoderm closest to and parallel with the notochord. Becomes segmented into somites
Intermediate: narrow column of mesoderm that is lateral to the paraxial mesoderm and gives rise to urogenital system
Lateral plate: thin plate of mesoderm lateral to intermediate mesoderm and splits to form lining of body cavities and mesoderm of most internal organs as well as limbs
Somitomeres
initial pairs of segments of mesenchyme that develop in the paraxial mesoderm
new ones are added caudally as the primitive streak regresses
11 pairs are kept at the caudal end
Somites
after 20 pairs of somitomeres have formed, the first somite form caudal to the 7th pair of somitomeres at the expense of the 8th.
Wavefront mechanism in somite differentiation
FGF-8 is increased in posterior primitive streak
RA is increased anteriorly and opposes FGF-8
this balance results in the cessation of somitogenesis
Mesp-2 is expressed because of this balance
Segmental clock and somite differentiation
At critical locations that will divide adjacent somites, lunatic fringe becomes concentrated at the future anterior border
C-hairy becomes concentrated at the future posterior border
Cells at the anterior border of an established somite express Eph A (receptor) and posterior cells express Eph B (ligand) creating a fissure.
Steps in somite differentiation
Formation of somitocoel
Formation of sclerotome
formation of dermomyotome and then separation into dorsal and ventral
Dermomyotome
Dorso-lateral part of a somite
Shh from notochord and Wnt from dorsal neural tube create balance that makes myotome commit to myogenetic lineage
Noggin inhibits BMP-4 which would normally inhibit myogenesis
BMP-4 suppresses myogenesis in verntrolateral dermomyotome and stimulates cells to migrate to limb bud
FGF from myotome signals production of scleraxis which causes formation of syndetome, the precursor of tendons
Intermediate mesoderm
Associated with the formation of the pronephros and mesonephros
Responds to BMP and activin -> becomes intermediate mesoderm -> expresses Pax2
Cranial and caudal extent is dependent on expression of Hox4 - Hox11
Which cells form the outflow tract of the heart?
Cells migrating through the anterior primitive streak
Which cells form the ventricles of the heart?
Cells migrating through the middle of the primitive streak
Which cells form the atria of the heart?
Cells migrating through the posterior primitive streak
Early heart formation
BMPs and FGFs act on the anterior visceral endoderm and cause the commitment to the heart-forming pathway.
Cells of the cardiac crescent (cells that migrated through the primitive streak) then express Nkx2-5, MEF2 and GATA4 which are necessary for heart formation.
What does the cardiogenic plate arise from?
splanchnic mesoderm
Which layer of a cardiac tube forms the myocardium?
Outer layer
Which layer of a cardiac tube forms the endocardium?
Inner layer
What is the source of pericardium and myocardial fibroblasts?
Proepicardial primordium
What circulatory arcs are present in a 4 week embryo?
Vitelline arc - vitelline vessels
Allantoic arc - allantoic vessels
Embryonic arc - dorsal aorta, aortic arches, anterior cardinal vein, common cardinal veins, posterior cardinal veins, atrium, ventricle and ventral aorta
Extraembryonic tissues
Amnion (inner cell mass: epiblast derivative) Yolk sac (inner cell mass: hypoblast derivative) Chorion (part of fetal maternal interface) Allantois (inner cell mass: interfaces with placenta via umbilical cord)
What makes up the fetal-maternal interface?
Placenta (trophoblast derivative)
Chorion (trophoblast derivative)
Previllous embryo (placenta)
No villi have been formed on the trophoblast
Primary villous stage (placenta)
Solid, cytotrophoblastic, ectodermal primary villi appear
Secondary villous stage (placenta)
Mesodermal cores appear within the primary villi
Tertiary villous stage (placenta)
Characterized by the appearance of blood vessels within the mesenchymal core of the secondary villi
Final development of the placenta
Cytotrophoblastic columns
Cytotrophoblastic shells formed by the expansion of the columns over maternal decidual cells
Anchoring villi
Maternal-Fetal blood flow pattern
Maternal blood enters intervillous space from spiral arteries
Exchange of materials between maternal blood in lacunae and fetal blood in the capillaries in the villi
Maternal blood retruns to maternal veins in the decidua basalis
Fetal blood travels to capillary beds within the placental villi via umbilical arteries and returns via umbilical vein
Functions of the placenta
Diffusion of oxygen and carbon dioxide
Diffusion of foodstuffs
Excretion of waste products
Early vs late placenta
Early: thick, low permeability, small surface area, minimal diffusion
Late: thin, high permeability, large surface area, increase in diffusion
Why can oxygenation occur despite the low pressure gradient between mother and fetus?
Fetal Hb has a higher affinity for oxygen
Fetal blood Hb concentration is 50% greater
Bohr effect (pH)
Human Chorionic Gonasotropin
Secreted by syncytial trophoblasts into maternal fluids
starts 8-9 days after ovulation
max secretion 10-12 wks of pregnancy
Functions of HCG
Prevents involution of corpus luteum
causes CL to increase secretion of progesterone and estrogen
causes increased growth in CL
exerts interstitial cell-stimulating effect on testes of male fetuses resulting in a production of testosterone
Progesterone
Secreted in small amounts by CL
Secreted in large amounts by placenta
Functions of progesterone
Causes decidual cells to develop in endometrium
Decreases contractility of pregnant uterus
Increases secretions of fallopian tubes and uterus
Helps prepare breasts for lactation
Human Chorionic Somatomammotropin
Secreted by placenta beginning 5th week of pregnancy
Functions to decrease insulin sensitivity and decreased utilization of glucose by the mother
Fetal alcohol syndrome
Causes: consumption of alcohol by mother during pregnancy
Symptoms: small head, wide set eyes, upturned nose, cognitive disabilities
Erythroblastosis fetalis (immune hydrops)
Causes: Rh negative mother, Rh positive fetus
Symptoms: hepatomegaly, splenomegaly, jaundice, anemia
Hydrops fetalis
Causes: heart or lung defects, chromosomal abnormalities. Can be immune or nonimmune. Also can be caused by hemolytic anemia
Symptoms: accumulation of edema fluid in fetus ->severe swelling, especially in abdomen, hepatomegaly and splenomegaly, difficulty breathing
Placenta previa
Causes: failure of placenta to migrate away from cervical opening
Symptoms: Attachment of th placenta to the wall of the uterus, covering the uterine outlet, bleeding after 20 wks pregnant
Hydatidiform mole
Causes: growth of an abnormal fertilized egg or an outgrowth of tissue from the placenta
Symptoms: uterus enlarges more rapidly, n/v, vaginal bleeding, very high blood pressure
What is the most common cause of neonatal mortality?
Congenital anomalies
Malformation
primary errors of morphogenesis. usually multifactorial, involving a number of etiological agents including genetic and environmental factors
Disruptions
disturbances in otherwise normal morphogenetic processes. Example: amniotic bands
Deformations
disturbances in otherwise normal morphogenetic processes. typically caused by abnormal biomechanical forces such as uterine constraints. Example: club foot
Sequences
series of events triggered by one initiating factor. An example is oligohydramnios (decreased amniotic fluid) which leads to a variety of events, including fetal compression and other problems stemming from fetal compression
Syndromes
constellations of congenital anomalies that are thought to be pathologically related but cannot be explained on the basis of a single local initial event. They are other caused by a single event such as a viral infection
Turner Syndrome
Genotype: X0 (45 chromosomes) Characteristics: female with underdeveloped sex characteristics low hairline broad chest folds on neck usually sterile usually normal intelligence
Poly-X Syndrome
Genotype: XXX Characteristics: Usually tall and thin often fertile most have normal intelligence
Prematurity and growth restrictions
second most common cause of neonatal mortality
Risk factors: preterm rupture of placental membranes, intrauterine infections, structural abnormalities in mothers reproductive tract, multiple gestation
Hazards: hyaline membrane disease, necrotizing enterocolitis, sepsis, interventricular hemorrhage, long term complications
Development of multilayered epidermis
Periderm: single layer of ectodermal cells formed by the end of the first month
Three- layered epidermis: formed by the end of the third month by activation of p63. Consists of the basal (germinative) layer, intermediate layer (inactivation of p63) and the superficial perdermal layer
What 2 layers does the intermediate layer of the 3 layer epidermis become?
Stratum spinosum (loss of integrins attached to the basal lamina, appearance of keratohyalin granules) and the stratum granulosum (interconnected by fillagrin)
Melanoblasts
from neural crest
migrate into dermis and then to epidermis
produce pigment by mid-pregnancy
Langerhans cells
derived from bone marrow
antigen-presenting cells
Merkel cells
from neural crest
slow-adapting mechano-receptors
Instructive induction
One germ layer instructs another on how to differentiate
Epidermal derivatives
Hair, nails, mammary glands
Commonalities: involve ectodermal-mesodermal interactions and inductions, begin as epidermal down growths into mesenchyme
How does prolactin contribute to the development of the mammary ducts?
induces milk protein and fat synthesis
How does oxytocin contribute to the development of the mammary ducts?
induces milk letdown
Common pathway of bone/cartilage differentiation
- mesenchyme is induced to enter the common pathway
- Production of N-cadherins promote mesenchymal cell condensation
- TGF-beta stimulates the synthesis of fibronectin and N-CAM
- Aggregated state of mesenchymal cells is stabilized
Membranous bone pathway
Requires transcription factors Runx-2 and Osx
Mesenchymal cells differentiate into osteoblasts
Permanent cartilage pathway
- mesenchymal condensation forms chondroblasts
- Sox-9 causes chondroblasts to secrete collagen II and cartilage matrix
- Sox-9 is continually expressed in permanent cartilage
Endochondral bone pathway
- Runx-2, ihh, and BMP-6 induce cartilage to undergo hypertrophy
- these cells then secrete bone proteins and vascular endothelial growth factor
- invading blood vessels erode the hypertrophic cartilage and bring in osteoblasts to replace cartilage with bone
Where is the centrum derived from?
ventral and medial parts of paired sclerotomes
Where are the neural arches derived from?
dorsal region of sclerotomes
What factors do the development of costal processes and ribs depend on?
Proximal development - expression of myotomic myogenic factors, Myf-5 and Myf-6
Distal development - BMP signals from somatopleural mesoderm
Which Hox gene creates the occipital-cervical boundary?
Hox3
Which Hox gene creates the cervical-thoracic boundary?
Hox6
Which Hox gene creates the attached floating ribs boundary?
Hox 9
Development of the axis and atlas
during formation cells form a proatlas anlage which contributes to the formation of the basioccipital bone and the dens of the axis which allows for rotation of C1 around C2.
Note the atlas does not have a centrum
Development of the clavicle
*one of the first bones to become ossified
arises from neural crest
follows intramembranous pathway
Neurocranium
- part of skull that surrounds the brain
- has a cartilaginous and membranous portion
- cartilaginous: origin of occipital, sphenoid, ethmoid, and parts of temporal
- membranous: origin of part of occipital, parietals, frontals, parts of temporals
Viscerocranium
- surrounds oral cavity and pharynx
- cartilaginous portion forms pharyngeal arch I and II
- membranous portion forms part of temporal, zygomatic, maxillary, nasal, lacrimal, palatine, vomer, pterygoid plates, mandible, tympanic ring
Formation and growth of chondrocranium/neurocranium
- basioccipital portion of chondrocranium is derived from parachordal cartilages and occipital sclerotomes
- other components of the original cartilages fuse to form final chondrocranium
- ossification centers form within the cartilage allow growth and are separated from each other by synchondroses
- elongation of primary ossification centers is due to Shh
- bones of the neurocranium arise as a result of inductive interactions characterized by transient appearance of type II collagen and cartilage-specific proteoglycan
- intersection of more than 2 bones form fontanelles
- fusion of sutures d/t expression of Noggin and absence of FGF-2 and BMP
Myogenic cell morphogenesis
- originates in somites
- resemble mesenchymal cells
- restricted to muscle-forming line
- mitotic cells kept labile by FGF and TGF-beta
Myoblast morphogenesis
derived from myogenic cells
post mitotic
Myotubes morphogenesis
- formed when myoblasts line up and adhere to one another
- requires Ca dependent CAMs
- involved in mRNA and protein synthesis
- characterized by appearance of actin, myosin, troponin and tropomyosin
- formation of myofibrils with sarcomeric arrangement
- nuclei move to periphery
Satellite cells
- located between sarcolemma and basal lamina of myofiber
- able to fuse with muscle fiber and provide for growth
- do not form new muscle fibers
- generally quiescent
- function as stem cells
- can become mitotic in times of stress via C-Met which is the receptor for HGF
- Give rise to myogenic precursor cells
What signals myogenic precursor cells to differentiate into embryonic myoblasts and causes the loss of their mitotic capability?
p21
Myogenic regulatory factors: MyoD family
- group of 4 helix-loop-helix TFs
- can convert non-muscle cells to cells capable of expressing muscle proteins
- forms dimer and binds to E box in enhancer region of myogenic genes, binding is enhanced by E12 and inhibited by id.
- Pax3 and Myf5 separately can activate MyoD
- increasing levels of MyoD and Myf5 result in expression of myoblast genes and expression of myogenin which results in the expression of myotube genes and Myf-6
- Myf6 leads to expression of myofiber genes
Origins of muscles of trunk
- epaxial muscles arise from dorsal lip of myotome
- epaxial tendons arise from syndetome layer within somites
- hypaxial tendons arise from ventral buds of myotome
- tendons of hypaxial muscles arise from lateral plate mesoderm
Origins of limb muscles
arise from ventrolateral dermomyotome
tendons arise from lateral plate mesoderm
Origins of muscles of head and neck
- Mostly derived from paraxial somitomeres
- extraocular muscles arise from prechordal plate
- most cranial musclulature is derived from the unsegmented paraxial mesoderm
- some cranial musculature (lower jaw) is derived from splanchnic mesoderm
Origins of cardiac muscle
- derived from splanchnic mesoderm
- early cardiac musculature does not express MyoD
- both cardiac muscle cells and skeletal muscle cells express MADs
- cardiac muscle cells begin to contract early
- maintain ability to divide by partially disassembling their contractile apparatus prior to cell division
- cardiac muscle cells remain as mononucleated cells and attach to each other via intercalated dics
Neural tube wall development
- early neural epithelium: simple cuboidal
- neural plate: simple columnar epitherlium
- early neural tube wall: pseudostratified epithelium, single layer of columnar cells with nuclei at varying heights. limiting membranes: basal lamina is external limiting membrane
- late neural tube wall: stratified epithelium
If metaphase plate is perpendicular to inner margin of neural tube
daughter cells remain proliferative
If metaphase plate is parallel to inner margin of neural tube
daughter cell closest to lumen will remain proliferative
daughter cell further from lumen will express notch receptor, become postmitotic, move to the external limiting membrane and become a neuroblast
Ventral signaling
notochord induces formation of the floor plate via Shh
Shh produced by the floor plate induces the formation of motor neurons
Dorsal signaling
ectoderm flanking the neural plate uses BMPs to induce snail-2 in the future neural crest and later to maintain Pax3 and Pax7 to create a dorsalizing effect
Pax 3 and 7 are suppressed by Shh from the floor plate
Isthmic organizer
- located between the mesencephalon and the metencephalon
- principle signaling moecule is FGF-8
- FGF-8 and Wnt-1 induce expression of En-1, En-2, Pax2, and Pax5 (concentration of these decreases away from the isthmic organizer)
- organizes and polarizes dorsal midbrain and cerebellum
Pax-7
related to formation of the alar plate
restricted by Shh
Pax-6
expressed in alar plate of diencephalon and is the master gene of eye formation
restricted by Shh
Formation of diencephalic-mesencephalic border
caused by reciprocal inhibition of Pax-6 and En-1
Diencephalon
P1-P3
Dorsal and ventral thalamus
P2-P3
Secondary rhombencephalon
cranial to P3
prochordal region of the neural tube
basal plate -> hypothalamus
alar plate -> cerebral cortex, basal nuclei, and optic vesicles
Motor axon growth
- axons grow out from the motor neuroblasts located in the basal plate of the spinal cord
- boundary caps created by neural crest cells maintain separation between central nervous system and peripheral nervous system
Formation of a sensory neuron
- cell bodies of sensory neurons are derviced from neural crest cells
- cells bodies of sensory neurons form sensory spinal ganglia
- axons grow from these cell bodies both toward the spinal cord and the periphery
- boundary caps maintain separation here
Where do sympathetic preganglionic motor neurons arise from?
intermediate (lateral) horns of gray matter
levels T1-L2
Where are autonomic ganglia derived from?
neural crest cells
Where are postganglionic autonomic neurons dervived from?
neural crest cells
Preganglionic sympathetic fibers can:
- ascend or descrend within the sympathetic chain to a more anterior or posterior ganglia and synapse with postganglionic neurons
- synapse immediately with postganglionic neurons
- pass more peropheral collateral ganglia to synapse with postganglionic neurons
Sympathetic postganglionic motor neurons
- are not myelinated
- may extend directly from collateral ganglia to target organs
- may reenter ventral root of the spinal nerve through gray ramus communicans
Differentiation of autonomic neurons
- BMPs determine whether migrating neural crest cells differentiate into autonomic neurons or other neural crest derivatives
- shift of determined autonomic neurons into sympathetic or parasympathetic is apparently d/t a multitude of TFs and involves type of NT to be used:
- sympathetic tend to be adrenergic
- parasympathetic tend to be cholinergic
Spinal cord organization
gray matter is centrally located in the form of anterior, posterior, and lateral horns situated around the central canal
Brain organization
in the deep brain, areas of gray matter are represented by basal nuclei. white matter is in the form of myelinated fiber tracts, generally superficial to gray matter
in the cerebrum and cerebellum, additional external areas of gray matter, the corticles, are built on top of the myelinated white matter tracts
What is the major topographical change of the myelencephalon from the spinal cord?
pronounced expansion of the roof plate to form the thin roof over the 4th ventricle
Expression of which set of gene seems to be responsible for the differentiation of specific nuclei in the myelencephalon?
Hox
Krox-20 -> rhombomeres 3-5
What are the major derivatives of the metencephalon?
pons (basal plate)
cerebellum (alar plate)
The cerebellum forms in the region of the rhombic lips (rhombomeres 1-8). The rhombic lips are the product of what inductive interation?
Roof plate and neural tube via BMP signaling
Migration of cells that will form the cortex in the cerebellar primordium
- granule cells migrate anteriorly along dorsal region of rhombomere 1
- granule cells migrate interiorly through perkinje layer
- purkinje cells migrate radially through granule cells
What are the superior cerebellar peduncles?
Massive fiber bundles between the cerebellum and the mesencephalon
What are the major derivatives of the alar plates of the mesencephalon?
Tectum - superior colliculi, inferior colliculi
Where is Otx-s located and how is it related to Shh?
It confines Shh to the basal part of the midbrain
Where do the cerebral peduncles form and what is their function?
ventrolateral region of the mesencephalon and they carry fibers between the cerebral hemispheres and the spinal cord
What are the major derviatives of the diencephalon?
epithalamus, thalamus, hypothalamus
What are the 3 patterning centers in the forebrain?
- rostral patterning center (FGF-8)
- Dorsal patterning center (BMPs and Wnts)
- Ventral patterning center (Shh)
Rachischisis
Complete failure of the neural tube to close
Spina bifida occulta
malformation of a vertebra with hair growth over the defect
Meningocele
protrusion of the meninges through a gap in the spine d/t a congenital defect
Myelomeningocele
spinal canal and spine do not close before birth, spinal cord is displaced
What causes formation of the somitocoel?
Expression of Wnt-6 by the ectoderm dorsal to the somite and decreased Snail, which causes mesenchymal cell to epithelial cell conversion
What causes formation of the sclerotome?
Release of Shh and noggin from the notochord resulting in expression of Pax-1 and Pax-9 in the ventral somite
What causes formation of the dermomyotome?
Wnt genes in the dorsal neural tube
What causes separation of the dermomyotome into dorsal and ventral?
Expression of Pax-3, Pax-7, paraxis
