Human Development Flashcards
Categories of Potentiality
Ability to differentiate other cells types
Totipotent - differentiate into all cell types (zygote, morula)
Pluripotent - many cell types (inner cell mass, epiblast)
Multipotent - restricted groups of cells (mesoderm, ectoderm, endoderm)
Unipotent - differentiation into a specific cell
Induced pluripotent stem cells
Differentiated cells that are pushed back to pluripotent status via iPS programming factors
Differential gene activity
- genes are reversibly turned on/off during different points in development for different gene expression
- cloning would not be possible if this was irreversible
- may be induced by programming factors (4 total)
Genomic equivalence
All cells have the same set of genes
Differential gene activity allows for differential gene expression between cells
First week progression of development following fertilization
Cleavage - blastomeres divide and shrink
Compaction - outer blastomeres form tight junctions, Inner blastomeres do not
Blastocyst formation - outer blastomeres form trophoblast layer, inner bastomeres form inner cell mass, fluid is pumped in to form blastocyst cavity
Hatching - growing blastocyst sheds zona pellucida to form floating blastocyst
Early implantation - cytotrophoblasts (inner layer of outer layer) and syncytiotrophoblasts (outer layer) form from Trophoblast, begin to implant into endometrium via metalloproteases, inner cell mass separates into hypoblast and epiblast, and produce protein and steroid hormones HCG (Human Chorionic Gonadotropin) which stops menstration
Hypoblast forms…
extra embryonic structures
Epiblast forms…
embryo proper
Chroriocarcinoma
Derived from syncytiotrophoblast, uses same mechanisms for implantation, most invasive cancer
Ectopic implantation
Implantation of blastocyte anywhere other than the uterus (uterine tubes, abdomen, etc.)
Normal implantation site of blastocyte
Fundus, or superior part of uterus between uterine tubes
Usually in posterior wall
Organogenic period
AKA embryonic period
Organ formation, most vulnerable to teratogens during this period
1-8 weeks
Fetal period
9-38 weeks
development of organs and organ systems
extensive growth
Lungs sufficiently developed at 24 weeks allowing premature births to survive with extensive clinical care
Post-natal development
Proliferation and Growth
Alveoli form in lungs
Closure of fetal shunts and vessels
Continued neuronal development
What factors play into pattern formation of cells
Cues from the environment
- cell-cell interactions, soluble factors (eg. growth factors), and extracellular matrix
Lineage : cell differentiation depends on cell of origin
Syndactyly
malformation due to unseparated digits
lack of apoptosis (morphogenetic error)
1st week of development
Ovulation (still in Meiosis II)
Fertilization (Finish of Oogenesis and Zygote formed)
Cleavage (Specialized cell division reducing cell size)
- Blastomeres form from cleavage (totipotent)
- Morula (day 4): loosely held mass of blastomeres
Compaction (day 5)(tight junctions, forms outer cell layer surrounding loosely held inner cell mass)
Blastocyst Formation (Fluid pumped in)
Hatching (Zona pellucida is shed & floating blastocyst)
Early Implantation
Syncytiotrophoblast
Releases matrix metalloproteases to break down extracellular matrix and aid in implantation
Also produce human chorionic gonadotropin to signal a stop to menstruation
2nd week of development
- Complete implantation
- Formation of primitive uteroplacental circulation
- no immunological rejection of fetus (Conceptus hides from mom’s immune system by reducing production of MHC Class I antigen) - Formation of bilaminar embryonic disk
- Formation of extraembryonic membranes/cavities
Prevalence of birth defects recognized by age 5
4-6%
Types of genetic screening regarding pregnancies
Carrier screening - determine carrier status in healthy people in high-risk population
Prenatal screening - identify if a fetus is at an increased risk of a defect
Newborn screening - detect genetic disorders that could be dangerous if left untreated
Contrast diagnostic testing and screening
Testing
- performed on at-risk population
- commonly expensive
- commonly has risk
- definitive
Screening
- performed on healthy patients
- inexpensive, quick, easy, reliable
- Defines at-risk population
- Not definitive
Amniocentesis
Invasive diagnostic test
Performed at 15 weeks and older
Samples amniotic fluid for genetic screening of cells
Chorionic villus sampling
Invasive diagnostic test
Performed in first trimester, 10-13 weeks
Samples placental tissue for genetic anomalies
First trimester screening
Performed between weeks 11-13
Ultrasound for measure of nuchal translucency (aneuploidy risk is continuous function of NT)
Blood work for serum markers (PAPP-A and hCG)
Assessing for:
Trisomy 21, 18 and 13
Second trimester screening
Performed between weeks 15-20
Testing for serum markers
Triple screen = msAFP, beta-hCG, uE3
Quad screen adds dimeric inhibin A
Abnormal maternal serum alpha-fetoprotein levels and associated risk
Low msAFP = higher risk for trisomy 21
High msAFP = higher risk for open neural tube defects
Note: twins can also cause elevated AFP, marker becomes less useful
Ultrasonography
Can be used diagnostically:
- confirm gestational age and number
- look for malformations
- confirm life
Or for screening:
- Structural abnormalities that associate with genetic abnormalies or aneuploidy
- AV canal defect and triploidy 21
- nuchal translucency
Cell free fetal DNA test
Isolate fetally derived DNA circulating in maternal plasma
-Shown to be accurate for high-risk groups, not as accurate for low-risk groups
Neuroectoderm
formed by chordin and noggin inhibition of BMP-4 signalling via Hensen’s node
notochord + somites
Bone morphogenetic protein-4
produced throughout embryonic plate
promotes ventral structure formation
blocked by chordin and noggin
Left-Right Body Axis formation
Hensen’s node cilia rotate counter-clockwise
concentration of nodal on left side of embryo
results in differential development
Laterality sequence
malformation in left-right orientation of organ
due to error in left-right body axis formation
Cephalic somitomeres
First 7, partially segemented area of paraxial mesoderm
Occipital somites
fully segmented somites
form base of skull
Trunk somites
fully segmented
forms vertebrae
Paraxial mesoderm
Mesoderm that segments into somitomeres and somites
Sclerotome
Formation induced by Sonic Hedgehog
Produces PAX1, starts cartilage/bone formation
Dermamyotome
formation induced by WNT
produces dermis, subcutaneous tissue and skeletal muscles
produces MYF5 - epaxial musculature
produces BMP-4 and MYOD - hypaxial musculature
Homeobox genes
Hox genes, arranged in a spacial pattern on chromosome
give positional information, determines somite segregation
Somatopleure
forms body wall
somatic mesoderm + ectoderm
Splanchnopleure
forms visceral wall
splanchnic mesoderm + endoderm
Neural crest cells
- neuroectoderm that mature into peripheral ganglia and Schwann cells
- migrate away from neural tube as they undergo epithelial-mesenchymal transformation
- form head and neck mesenchyme (branchial arch mesenchyme)
Neural tube formation
- ectoderm above notochord thickens - neural plate
- Elevation of neural folds from Neural groove
- lateral edges of neural plate (neural folds) will fold up to form neural tube (on top of notochord)
- microtubules elongate cells and apical actin induces folding - neural folds and neural groove
- changes in cell shape lead to tube formation
- neural folds meet and form neural tube
- Formation is cranial to caudal ( brain is thicker then spine)
- Openings in both cranial and caudal ends of tube are Neuropores
Teratogen
Compound that can form congenital problems
Teratoma
Tumor formed from differentiation w/ loss of pattern formation
Limb Development
- Specification of little vs. great digit
- Zone of polarizing activity: group of cells that induce lower digit to form in both hind & fore-limb (located at posterior side of limb)
- Produces soluble factor :Sonic Hedgehog (Shh) which induces adjacent cells to form little digit
- Cells in hind and forelimb react differently to the same factor due to differences between these cells
Morphogenesis
Process that cause an organism to develop its shape
- change in cell shape/size
- gain/loss of cell-cell adhesion
- Migration (mvmt of individual cell w/ respect to others)
- Ingression (mvmt from surface->interior of embryo)
- Egression (mvmt from interior to surface of embryo)
- Delamination (mvmt out of epithelial sheet aka single to multiple layers)
- Interclation (mvmt into a single layer of epithelial sheet = merging)
- Condensation (Mesenchymal to epithelial)
- Dispersal (Epithelial to mesenchymal)
- Epiboly (Spreading of sheets)
Placenta Previa
- Implantation near the internal os (opening of cervix) of uterus
- Placenta will cover the internal os
- Placenta may separate from uterine wall, Requires C-section
Tubal Implantation
- Most common ectopic site
- delayed transport along uterine tube which may rupture leading to potential death of mother and fetus
Ovarian and Abdominal Implantation
- fertilized zygote doesn’t make it to the uterine tube
- Lithopedian: fetus becomes calcified if remains in abdomen
Desidua Reaction
Stroma in the endometrium will become hydrated and cells fill w/ glycogen and lipds
Formation of Bilaminar Embryonic Disk
(2nd week of dev.)
- Inner cell mass cells reorganize to form to layers
- upper epiblast
- lower hypoblast - thickening of one end of the hypoblast layer defines cranial end of bilaminar embryonic disk known as the Anterior Visceral Endoderm
Formation of Extraembryonic membranes and cavities
- All extraembryonic cavities form by end of 2nd week
- Bilaminar embryonic disk formation creates amniotic and blastocyst cavity
- Inner cell mass cells attached to cytotrophoblasts become Amniocytes
- Exocoelomic Membrane forms from migration of hypoblast cells around blastocyst cavity making the primary yolk sac
- Extraembryonic mesoderm forms between the cytotrophoblast and the exoceolomic membrane and also the cytotrophoblast and amniocytes, THUS thickening walls of conceptus
- Cavitation of extramembryonic mesoderm form extraembryonic coelom
- Cavity is surrounded by inner splanchnic mesoderm to outer somatic mesoderm
- Connecting stalk connects somatic and splanchnic
Allantois
- Vestigial structure in humans, where the secondary yolk sack projects into the connecting stalk
- Caudal end, should disappear but if doesn’t could lead to malformations
Chorion
Combination of Syncytiotrophoblast, Cytotrophoblast, and Somatic extraembryonic mesoderm
Molar Pregnancy
- Abnormal embryonic development w/ excess development of trophoblast - extraembryonic structures
- Genome entirely paternal (Dispermy or sperm duplication with female pronucleus lost)
- suggests paternal genome drives extraembryonic and trophoblast development while maternal drives embryonic (inner cell mass) deviation
Gastrulation
Process by which 3 germtypes are formed in 3rd week
- Ectoderm (skin and nervous system)
- Endoderm (lining of GI tract)
- Mesoderm (Muscle, Heart, & Skeleton)\
- ALL THREE FORMED FROM EPIBLAST
Gastrulation Process
- Occurs through primitive streak (thickened, caudal epiblasts)
- Ingression of epiblasts through P. Streak forms the P. Groove
- Cranial end of P. streak there is a large knot known as HENSEN’S NODE
- depression in Hensen’s node is the P. Pit
- Ingression of epiblasts through P. Groove forms Mesoderm
- Epiblasts the ingress through the P. Groove replace hypoblasts to form Endoderm
- Epiblasts that don’t ingess form Ectoderm
Epithelial-Mesenchymal Transformation
Week 3
- occurs as epiblasts ingress through P. Groove and become Mesenchymal cell
- Some epiblasts might pass through the groove to replace Hypoblasts, these cell transform to Mesenchymal, and then transform into Epithelial cells in order to form the endoderm
Migration of _______
- Mesoderm midline forms the Notochord
- Mesoderm migrating laterally and Caudally forms Cardiogenic Region
- Will not have mesoderm in Oropharyngeal membrane (mouth) and cloacal membrane (future anus)
Sacrococygeal Teratoma
Lack of Primitive streak regression at end of 4th week
Neural Tube Defects
- high levels of AFP
- Spina Bifida
- Spina Bifida Occulta: Neural tube closes but vertebral arch hasn’t closed (least severe)
- Meningocele: incomplete closing of neural tube, protrusion of meninges where there is incomplete closing (polyp)
- Meningomyelocele: (most severe) meninges and spinal cord tissue protrude, neural tube hasn’t closed
Anterior-Posterior Axis Formation
- Nodal Expressed: throughout epiblast, nodal promotes formation of Hensen’s node and P. streak
- Nodal = transformation Growth Factor (signals for caudal development)
- Anterior Visceral Endoderm: secretes Cerberus and Lefty that block nodal signaling, preventing posterior structure formation in cranial region
Induction of Primary Body Axis
- Induction: group of cells determine development of another group of cells
- BMP-4 (Bone Morphogenetic Protein-4) expressed throughout embryonic disk, promotes ventral structures
- Hensen’s node: secretes factors the block BMP-4 (chordin and noggin)
- Epiblasts that moves thru Hensen’s node are induced to produce chordin & noggin
- Lack of BMP-4 signaling allows cells to become neuroectoderm
Paraxial Mesoderm
- Segments into Somitomeres and Somites
- Cranio->Caudal development
- Cephalic Somitomeres: first 7 segments that will form the skull are partially segmented (somatomeres)
- Occipital Somites: fully segmented somites- will form bone of skull
- Trunk Somites: fully segmented somites the will form vertebrae
- last 4 somites will disappear during development
Somites
- Epithelial cells that transformed from mesenchyme cells
- Sclerotome: forms the axial skeleton
- Dermamyotome: forms dermis, subcutaneous and myotome
- Myotome: forms skeletal muscle
- each somite induces a spinal nerve to form
Intermediate Mesoderm
- Forms part of urogenital system (Nephrotomes forms in the caudal region)
Lateral Plate Mesoderm
- will split into somatic mesoderm, and splanchnic mesoderm to form embryonic coelom
- Somatopleure: somatic mesoderm and ectoderm that will form body wall
- Splanchnopleure: splanchnic mesoderm and endoderm will form visceral wall
- Embryonic Coelom: forms body cavities (pleural, pericardial, peritoneal) embryonic and extraembryonic coelom connect at midline of body
Mesoderm Groups
N - Notochord
P - Paraxial Mesoderm
I - Intermediate Mesoderm
L - Lateral Mesoderm
Haloprosencephaly
Single brain ventricle, cyclopedia, thought to occur in 3rd week of development possibly due to alcohol consumption effecting gastrulation
Pleiotrophy
Single causative agents results in abnormalities of more than one organ system, may arise at different times during intrauterine life
Syndrome
Collection of major/minor abnormalities that occur together, predictable, etiology often known
Association
Anomalies that frequently occur together but are not predictable and etiology is not known
Sequence
Group of related anomalies stemming from a single initial anomaly
eg. spina bifida —> lower extremity problems
Malformation
altered fetal development of a structure due to intrinsic factors, such as genetic/epigenetic mutations or teratogens
Deformation
Altered fetal development due to an external force
Disruption
Normally growing structure stops developing due to a disrupting factor
eg. amniotic bands
Dysplasia
Intrinsic cellular architecture of a tissue is not maintained throughout development
