DivisionsDivisions ofof embryologyembryology
GeneralGeneral eembryologymbryology Gametogenesis: conversion of germ cells into male and female gametes 1st week of development: ovulation to implantation 2nd week of development: bilaminar germ disc 3rd week of development: trilaminar germ disc 3rd to 8th week: embryonic period 3rd month to birth: fetus and placenta SpecialSpecial eembryologymbryology Skeletal system Cardiovascular system Respiratory syste m Nervous system, etc …. systems GASTRULATION (Gr., belly ) BBilaminarilaminar diskdisk →→ trilaminartrilaminar diskdisk
TheThe embryoembryo hashas reachedreached aa pointpoint ofof balancebalance inin itsits efeffortsforts toto :: draw nourishment from the mother (trophoblast layers and their derivatives) to be protected against cellular assault (several ensheathing layers & protective cavities) to harbor enough of its own food (secondary yolk sac ) TimeTime toto movemove –– thethe innerinner cellcell massmass derivativesderivatives differentiatedifferentiate intointo thethe threethree functionalfunctional cellcell layerslayers ofof lifelife outer layer → protective and sensitive inner layer → energy -absorbing connective layer between them → contractile movement GastrulationGastrulation startsstarts withwith primitiveprimitive streakstreak
cut
trophoblast 90 ° rotation PrimitivePrimitive streakstreak –– dayday 1414 Formed by cells of the epiblast which choose one of the two fates: pass deep to the epiblast layer to form the populations of cells within the embryo endoderm (formed by replacement of hypoblast by invading epiblas t cells) mesoderm (once definitive endoderm is established, inwardly movi ng epiblast forms mesoderm) remain on the dorsal aspect of the embryo to become the embryonic ectoderm Formation of the primitive streak is induced by the underlying visceral hypoblast (a narrow groove with slightly bulging regions on either side) Cells of the intra embryonic mesoderm migrate between ectoderm & endoderm until they establish contact with the extra embryonic mesoderm covering yolk sac and amnion Mesodermal cells cannot penetrate the adhesion at the head end of the embryo called bucco pharyngeal membrane, they cannot penetrate the adhesion at the tail end called cloacal membrane , and they cannot displace the notochord cells that have streamed out of the primitive streak and remained in the midline StructuresStructures associatedassociated withwith thethe primitiveprimitive streakstreak
Primitive (Hensen ’s) node - the cephalic end of the primary streak ; a slightly elevated area surrounding the small primitive pit Primitive pit – invagination in the center of the primitive node Primitive groove - the lower midline portion of the primitive streak
The process by primitive node/pit which cells become part of the streak and then migrate away from it beneath the epiblast is termed ingression PrimitivePrimitive streakstreak && itsits associatedassociated structuresstructures
Primitive groove N.B.!!!N.B.!!!
Epiblast is the source of all of the germ layers and cells in these layers will give rise to all of the tissues and organs in the embryo DirectionsDirections ofof streakstreak cellscells migrationmigration
Buccopharyngeal cranial membrane
pit
streak caudal TheThe positionposition andand timetime ofof ingressioningression throughthrough primaryprimary streakstreak directlydirectly affectaffect ss thethe developmentaldevelopmental fatefate ofof cellscells
Cells that ingress through the primitive node give rise to the axial cell lines, the prechordal mesoderm and notochord Primitive streak rostral node portion → cells for the lateral Notochord halves of the somites Primitive streak middle portion → lateral plate mesoderm streak Primitive streak caudal
Mesoderm (lateral) portion → primordial germ cells, extraembryonic Primordial germ cells mesoderm mesoderm StructuresStructures inin thethe cranialcranial endend ofof thethe embryonicembryonic diskdisk
BBuccopharyngealuccopharyngeal membranemembrane a small region at the cranial end of the embryonic disc , cranial from the prechordal plate tightly adherent ectoderm and endoderm cells represents the future opening of the oral cavity breaks down in the 4th week, opening the oral cavity to the pharynx PPrechordalrechordal (prochordal)(prochordal) plateplate forms between the tip of the notochord and the buccopharyngeal membrane derived from some of the first cells that migrate through the primitive node in a cephalic direction important in forebrain induction BuccopharyngealBuccopharyngeal membranemembrane cranial caudal Primitive streak establishes cranial/caudal; left/right body asymmetry, and body axes
A amnionic cavity
Y ectoderm
foregut endoderm
buccopharyngeal membrane
The buccopharyngeal membrane and consists of ectoderm opposed to endoderm PrechordalPrechordal plateplate
In the rostral midline, the ectoderm and endoderm are opposed. The endoderm in this location forms the prechordal plate (a thickening of the endoderm) ectoderm Prechordal plate is located at the anterior end of the notochord, but not reaching the rostral extremity of the embryo
endoderm NotochordNotochord ((= chordachorda dorsalis)dorsalis) - specialization of the mesoderm
The notochord extends A in the midline from the prechordal plate , caudally Y to the primitive streak cranial saggital section caudal ectoderm
Prechordal plate Notochord
endoderm NotochordNotochord formationformation
Prenotochordal cells coming from the primitive pit move in cranial direction until they reach the prechordal plate Prenotochordal cells mix with hypoblast cells to form a temporary notochordal plate As hypoblast is replaced by endoderm, notochordal plate cells detach from the mesoderm endoderm → definitive notochord Notochord extends from buccopharyngeal membrane to primitive pit – cranial end forms first, caudal - later NotochordNotochord formationformation cranial Notochord extends from buccopharyngeal membrane to primitive pit – cranial end forms first, caudal - later
caudal
Detachment of notochordal plate cells from the endoderm NotochordNotochord formationformation NotochordNotochord underliesunderlies thethe neuralneural tubetube andand servesserves asas thethe basisbasis forfor thethe axialaxial skeletonskeleton
Molecular Biology of the Cell (© Garland Science 2008) Neurenteric canal
A
Y
cranial
caudal
Temporary connect ion between the amniotic and yolk sac cavities at the point where the primitive pit forms an indentation in the epiblast Cloacal membrane
A
Y
cranial caudal
Formed at the caudal end of the embryonic disc. Similar in structure to the buccopharyngeal membrane → tightly adherent ectoderm and endoderm cells with no intervening mesoderm Breaks down in the 7th week → anus & urinary/reproductive systems openings AAllantoisllantois When the cloacal membrane appears (day 16), the posterior wall of the yolk sac allantois stalk forms a small diverticulum that extends into the epiblast connecting stalk → allantois A little out -pocketing of the hypoblast caudal end of yolk sac trapped in the connecting caudal trapped in the connecting cranial stalk This blind pouch is called the allantois (Gr., sausage -shaped ) Importance structural base for the umbilical cord becomes part of the urinary bladder Establishment of body axes takes place before and during the period of gastrulation
Body axes anteroposterior dorsoventral left-right Anteroposterior axis is signaled by cells at the anterior (cranial) margin of the embryonic disc → anterior visceral endoderm (AVE) expresses genes essential for head formation Left-right sidedness and dorsoventral axis formation are orchestrated by genes expressed in the primitive streak and pit
cranial
caudal Growth of the embryonic disc
Initially flat and almost round, embryonic disk gradually becomes elongated with a broad cephalic and a narrow caudal end Expansion of the embryonic disc occurs mainly in the cephalic region; the region of the primitive streak remains more or less the same size cranial In the cephalic part, germ layers begin their specific differentiation by the middle of the 3rd week, whereas in the caudal part, differentiation begins th neural by the end of the 4 week plate
caudal Gastrulation may be disrupted by genetic abnormalities and toxic insults
In caudal dysgenesis (sirenomelia), insufficient mesoderm is formed in the caudal-most region of the embryo. Because this mesoderm contributes to formation of the lower limbs, urogenital system, and lumbosacral vertebrae, abnormalities in these structures ensue Development of trophoblast in 3 rd week
day 13
Mesodermal cells penetrate the core of primary villi and grow toward the decidua → secondary villi
day 13 day 15 Development of trophoblast in 3 rd week
By the end of 3 rd week, mesodermal cells in the core of the villus begin to differentiate into blood cells and vessels, forming the villous capillary system → tertiary (definitive, placental) villi Development of trophoblast – end of 3 rd week
Cytotrophoblastic cells surround the trophoblast entirely (form outer shell) and are in direct contact with the endometrium The outer shell gradually surrounds the trophoblast entirely and attaches the chorionic sac firmly to the maternal endometrial tissue Embryo is suspended in the chorionic cavity by means of the connecting stalk Development of trophoblast – end of 3 rd week
Maternal vessels ↓ Intervillous space ↓ Trophoblast ↓ Villous capillary ↓ Chorionic plate vessels (=extraembryonic ↓ somatopleuric mesoderm) Intraembryonic vessels
Maternal vessels penetrate the cytotrophoblastic shell to enter intervillous spaces, which surround the villi. Capillaries in the villi are in contact with vessels in the chor ionic plate and in the connecting stalk, which in turn are connected to intraembryonic vessels StemStem vsvs terminalterminal tertiarytertiary villivilli
stem villus
terminal villus
Stem (anchoring ) villi - extend from the chorionic plate to the endometrium Terminal (f ree) villi - branch from the sides of stem villi → through them exchange of nutrients will occur DivisionsDivisions ofof embryologyembryology
GeneralGeneral eembryologymbryology Gametogenesis: conversion of germ cells into male and female gametes 1st week of development: ovulation to implantation 2nd week of development: bilaminar germ disc 3rd week of development: trilaminar germ disc 3rd to 8th week: embryonic period 3rd month to birth: fetus and placenta SpecialSpecial eembryologymbryology Skeletal system Cardiovascular system Respiratory syste m Nervous system, etc …. systems 3rd -8th week → embryonic period (=period of organogenesis)
Each of the 3 germ layers, ectoderm, mesoderm, and endoderm, gives rise to a number of specific tissues and organs By the end of the 2nd month, the main organ systems have been established → the major features of the external body form are recognizable EctodermEctoderm derivativesderivatives
SurfaceSurface ectodermectoderm skinskin (epidermis,(epidermis, hair,hair, nails,nails, glands)glands) anterioranterior pituitarypituitary earear (receptor(receptor apparatusapparatus ofof innerinner ear)ear) nosenose (olfactory(olfactory epithelium)epithelium) NeuroectodermNeuroectoderm neuralneural tubetube –– centralcentral nervousnervous system,system, eyeeye (iris,(iris, ciliary)ciliary) neuralneural crestcrest –– cellscells outsideoutside CNSCNS NeurulationNeurulation
DifferentiationDifferentiation ofof aa subsetsubset ofof neuroectodermalneuroectodermal cellscells intointo neuralneural precursorprecursor cellscells NeuralNeural plateplate NeuralNeural foldfold NeuralNeural tubetube KeyKey consequencesconsequences ofof neurulationneurulation formationformation ofof neuralneural tubetube –– centralcentral nervousnervous systemsystem formationformation ofof neuralneural crestcrest -- allall neuronsneurons outsideoutside ofof thethe brainbrain andand spinalspinal cordcord ++ numerousnumerous disperseddispersed cellcell typestypes Neural plate → neural groove
NotochordNotochord andand prechordalprechordal mesodermmesoderm inducesinduces thethe overlyingoverlying ectodermectoderm toto thickenthicken andand formform thethe neuralneural plateplate (~day(~day 18)18) NeuralNeural plateplate graduallygradually expandsexpands towardtoward thethe primitiveprimitive streakstreak →→ atat endend ofof 33 rd weekweek thethe cranial primitiveprimitive streakstreak runsruns ¼¼ ofof thethe embryoembryo TheThe edgesedges ofof thethe plateplate (( neuralneural foldsfolds )) riserise andand formform aa concaveconcave areaarea knownknown asas thethe neuralneural streak neural groovegroove (~day(~day 20)20) plate
caudal Neural groove
The ectoderm can be neural ectoderm distinguished as neural ectoderm that comprises the central nervous system, and surface ectoderm that will cover the outside of the body.
surface ectoderm Neural groove → tube
NeuralNeural foldsfolds approachapproach eacheach otherother inin thethe midlinemidline wherewhere theythey fusefuse (~day(~day 21)21) TThehe tubetube pullspulls awayaway fromfrom thethe ectodermectoderm aboveabove itit toto becomebecome embeddedembedded underneathunderneath thethe ectodermectoderm
Ectoderm NeuralNeural tubetube formationformation
Neural folds fusion begins in the cervical region (level of 5 th somite) and proceeds cranially and caudally Until fusion is complete, the extremities of the neural tube communicate with the amniotic cavity by way of the cranial and caudal neuropores CranialCranial (anterior)(anterior) neuroporeneuropore closureclosure
A frontal view illustrates the closing anterior neuropore and the stomodeum (primitive oral cavity) CaudalCaudal (posterior)(posterior) neuroporeneuropore closureclosure
The posterior neuropore closes about 2 days after the anterior neuropore, when the embryo is tightly curved ventrally and an upper limb bud is evident. Disorders of Primary Neurulation Neural Tube Defects
Craniorachischisis CraniorachischisisCraniorachischisis totalistotalis AnencephalyAnencephaly MyeloschisisMyeloschisis EncephaloceleEncephalocele MyelomeningoceleMyelomeningocele ArnoldArnold --ChiariChiari malformationmalformation
Armstrong D, Halliday W, Hawkins C, Takashima S. Pediatric Volpe JJ. Mental Retardation And Developmental Disabilities Neuropathology . Springer 2007 Research Reviews 6: 1–5 (2000) AnencephalyAnencephaly
Anencephaly is characterized by failure of the cranial neuropore to fuse NeurulationNeurulation isis accompaniedaccompanied byby embryoembryo foldingfolding
yolk sac NeuronalNeuronal specificationspecification withinwithin thethe neuralneural tubetube isis orchestratedorchestrated byby signalssignals fromfrom notochordnotochord && floorfloor platplatee NeuralNeural crestcrest
As the neural folds elevate and fuse, cells at the dorsal border (=crest) of the neural folds begin to dissociate from their neighbors NeuralNeural crestcrest cellscells migratemigrate awayaway fromfrom thethe neuralneural tubetube
Following the closure of the trunk neural folds, the neural crest cells leave the dorsal aspect of the neural tube Neural crest cells leave the neuroectoderm by active migration and displacement to enter the underlying mesoderm NeuralNeural crestcrest cellscells migrationmigration pathwayspathways
dorsal pathway
ventral pathway
Molecular Biology of the Cell (© Garland Science 2008) NeuralNeural crestcrest derivativesderivatives
MostMost ofof thethe sensorysensory componentscomponents ofof thethe PNSPNS SensorySensory neuronsneurons ofof cranialcranial andand spinalspinal sensorysensory ganglgangliaia AutonomicAutonomic gangliaganglia andand thethe postganglionicpostganglionic autonomicautonomic neuronsneurons MuchMuch ofof thethe mesenchymemesenchyme ofof thethe anterioranterior headhead andand necneckk MelanocytesMelanocytes ofof thethe skinskin andand oraloral mucosamucosa OdontoblastsOdontoblasts (cells(cells responsibleresponsible forfor productionproduction ofof ddentin)entin) ChromaffinChromaffin cellscells ofof thethe adrenaladrenal medullamedulla CellsCells ofof thethe arachnoidarachnoid andand piapia matermater SatelliteSatellite cellscells ofof peripheralperipheral gangliaganglia SchwannSchwann cellscells
SurfaceSurface andand neuralneural ectodermectoderm cellscells havehave aa differentdifferent appearanceappearance
Note the squamous (flat) surface ectodermal cells and the columnar cells comprising the neural tube EctodermalEctodermal placodesplacodes
SSmallmall locallocal aggregatesaggregates ofof ectodermectoderm remainingremaining withinwithin thethe surfacesurface ectodermectoderm →→ passpass deepdeep toto thethe surfacesurface ectodermectoderm afterafter neurulationneurulation GGiveive riserise toto neuralneural 77 nonnon neuralneural structuresstructures OOpticptic placodesplacodes →→ lenslens ofof thethe eyeeye DentalDental placodesplacodes –– enamelenamel ofof teethteeth OticOtic placodesplacodes –– labyrinthlabyrinth ofof thethe innerinner earear AAdenohypophysealdenohypophyseal placodeplacode –– anterioranterior pituitarypituitary OlfactoryOlfactory placodeplacode –– olfactoryolfactory epithelialepithelial cellscells MesodermMesoderm
Epiblast cells ingress through the primitive streak between ectoderm & endoderm → become elongated → detach from the epiblast MesodermMesoderm derivativesderivatives Mesoderm cells coming from primitive node and rostral primitive streak form the paraxial mesoderm (day 17) Intermediate mesoderm – lateral to the paraxial, for a short stretch of the embryo’s length Mesoderm cells coming from the middle to caudal streak form the lateral plate mesoderm → divided into two layers somatic (parietal) mesoderm - continuous with mesoderm covering the amnion splanchnic (visceral) mesoderm - continuous with mesoderm covering the yolk sac MainMain mesodermalmesodermal divisionsdivisions -- dayday 2222
Neural folds
TheThe intraembryonicintraembryonic mesodermmesoderm differentiatesdifferentiates intointo paraxialparaxial ,, intermediateintermediate ,, andand laterallateral plateplate portionsportions MesodermMesoderm partitionpartition –– paraxialparaxial
ParaxialParaxial mesodermmesoderm accumulatesaccumulates underunder thethe neuralneural plateplate withwith thinnerthinner mesodermmesoderm laterally.laterally. FormsForms 22 thickenedthickened streaksstreaks runningrunning thethe lengthlength ofof thethe embryonicembryonic discdisc alongalong thethe rostrocaudalrostrocaudal axis.axis. DuringDuring thethe 3rd3rd week,week, paraxialparaxial mesodermmesoderm beginsbegins toto segmentsegment MesodermMesoderm partitionpartition –– intermediateintermediate && laterallateral
Intermediate mesoderm connects paraxial and lateral plate mesoderm Lateral plate mesoderm layers line a newly formed cavity, the intraembryonic cavity (coelom), which is continuous with the extraembryonic cavity on each side of the embryo ParaxialParaxial mesodermmesoderm developmentdevelopment -- segmentationsegmentation
Early 3 rd week – paraxial mesoderm forms paired ball-like structures → segments (=somitomeres) – by day 20 organize into somites Somite formation starts cranially → caudally at a speed of 3 pairs/day → at 5 th week 42-44 pairs (4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 8-10 coccygeal pairs) Occipital & coccygeal later disappear Somite number correlates to age SomiteSomite -- dayday 2323
intraembryonic Neural tube coelom
TheThe paraxialparaxial mesodermalmesodermal cellscells inin thethe trunktrunk becomebecome organizedorganized intointo somitessomites SomitesSomites areare visiblevisible asas ballball --likelike structuresstructures -- dayday 2828
somite somite SomiteSomite differentiationdifferentiation -- dayday 2727
Notochord Notochord Each somite differentiates, forming a dermomyotome (dermatome + myotome) and a sclerotome Sclerotome cells build the ventral and medial walls of the somite, lose their compact organization, surround the notochord Dermomyotome cells build the dorsolateral walls of the somite – divide into dermatome & myotome Dermomyotome cells form dermatome & myotome – day 28
The myotomes are comprised of muscle cells, some of which migrate into the body wall and limbs Dermatome cells lose their epithelial configuration and spread out under the overlying ectoderm → will form dermis and subcutaneous tissue of the skin SclerotomeSclerotome differentiationdifferentiation -- dayday 2828
Notochord
The sclerotomes are comprised of cells that form the vertebrae. In the midline, these cells condense around the notochord SclerotomeSclerotome differentiationdifferentiation -- weekweek 99
Notochord
The sclerotomes cells differentiate into cartilage and bone, and surround the notochord Within the intervertebral disks that form between the vertebral bodies, the notochord persists as the nucleus pulposus Each myotome and dermatome retains its segmental innervation no matter where the cells migrate
Each somite forms its own sclerotome → cartilage and bone component myotome → segmental muscle component) dermatome → the segmental skin component Each myotome and dermatome has its own segmental nerve component
segment RegulationRegulation ofof bodybody planplan byby HoxHox genesgenes
Homeobox genes are known for their DNA binding motif - the homeobox They code for transcription factors that activate cascades of genes regulating phenomena such as segmentation and axis formation
Kandel, Schwartz, Jessell; Principles of Neural Science, 4 th ed. www.nobelprize.org DevelopmentDevelopment ofof intermediateintermediate mesodermmesoderm
Temporarily connects paraxial mesoderm with the lateral plate mesoderm Differentiates into urogenital structures cervical and upper thoracic regions → nephrotomes (segmented cell clusters) more caudally → nephrogenic cord (unsegmented mass of tissue) DevelopmentDevelopment ofof intermediateintermediate mesodermmesoderm
21 days 25 days DevelopmentDevelopment ofof laterallateral plateplate mesodermmesoderm
day 22
The lateral plate mesoderm splits into somatic (parietal) and splanchnic (visceral) layers Between them – the intraembryonic coelom DevelopmentDevelopment ofof laterallateral plateplate mesodermmesoderm
day 23
Somatic mesoderm → ventral & lateral body wall and limbs Splanchnic mesoderm → wall of the viscera (heart, hollow organs) LateralLateral plateplate mesodermmesoderm contributescontributes toto serousserous membranesmembranes aroundaround internalinternal organsorgans
day 21 day 28
Somatic mesoderm → peritoneal, pleural, and pericardial cavities Splanchnic mesoderm → serous membrane around each organs TheThe spacespace betweenbetween thethe twotwo layerslayers ofof laterallateral plateplate mesodermmesoderm formsforms thethe intraembryonicintraembryonic coelomcoelom
day 23 EvolutionEvolution ofof thethe intraembryonicintraembryonic coelomcoelom
day 21 day 28
Splanchnic mesoderm layers are continuous with Communicates with somatic layers as a double -layered membrane → extraembryonic coelom No communication with extraembryonic coelom Mesoderm vs mesenchyme
Mesoderm refers to cells derived from the epiblast and extraembryonic tissues Mesenchyme refers to loosely organized embryonic connective tissue regardless of origin Vessel and blood cell form from a common precursor – the hemangioblast
TypesTypes ofof bloodblood vesselvessel productionproduction vasculogenesisvasculogenesis –– fromfrom hemangioblastshemangioblasts →→ angioblastsangioblasts angiogenesisangiogenesis –– fromfrom prepre --existingexisting vesselsvessels Hemangioblasts appear in mesoderm surrounding the wall of the yolk sac at mid-3 weeks of development
A
Mesoderm cells form Y extraembryonic splanchnopleure form Day 19 blood islands Center of blood islands form HSC → blood cells Periphery of blood islands form angioblasts → blood vessels Blood islands are transitory
Neural tube Notochord The definitive HSC arise from mesoderm surrounding the aorta in a site called A AGM region ↓ Liver ↓ M Aorta-Gonad-Mesonephros-Region (AGM) G Bone marrow FormationFormation ofof thethe cardiogeniccardiogenic fieldfield
Cardiac progenitor cells lie in the epiblast, A immediately lateral to the primitive streak Y Migrate through the streak → position in front of the neuroectoderm at day 18 the intraembryonic cavity over the cardiogenic field later develops into the pericardial cavity EndodermEndoderm derivativesderivatives
CoversCovers thethe ventralventral surfacesurface ofof thethe embryoembryo andand formsforms thethe roofroof ofof thethe yolkyolk sacsac Initially forms the epithelial lining of the primitive gut foregut - temporarily bounded by the buccopharyngeal membrane – after 4 th week a connection is formed between the foregut and the amnionic cavity midgut - temporarily communicates with the yolk sac by way of a broad stalk, the vitelline duct hindgut - temporarily bounded by the cloacal membrane – after 7 th week a connection is formed between the hindgut and the amnionic cavity (anus) Progressive cephalocaudal folding of the embryo → continuously larger portion of the endoderm-lined cavity is incorporated into the body of the embryo proper
day 23 day 28
midgut hindgut foregut TheThe passagepassage betweenbetween midgutmidgut && yolkyolk sacsac becomesbecomes progressivelyprogressively thinnerthinner
day 21 day 28 Derivatives of the endodermal germ layer
day 25 day 35
Partial incorporation of the allantois into the body of the embryo → cloaca Derivatives of the endodermal germ layer
Early structures epithelial lining of the primitive gut epithelial lining of the intraembryonic portions of the allantois and vitelline duct Later structures epithelial lining of the respiratory tract; parenchyma of the thyroid, parathyroids, liver, and pancreas reticular stroma of the tonsils and thymus; epithelial lining of the urinary bladder and urethra epithelial lining of the tympanic cavity and auditory tube DerivativesDerivatives ofof thethe 33 germgerm layerslayers
Endoderm Mesoderm Ectoderm o lining of digestive o muscle o nervous system and system o outer covering of brain o lining of respiratory organs o epidermis and related system o excretory system structures o liver o gonads o pancreas o circulatory system o glands o bones and cartilage o circulatory system o dermis
GermGerm layerlayer stemstem cellscells andand theirtheir derivativesderivatives
www.abcam.com The embryonic period is divided into 23 Carnegie stages based on external and internal morphological criteria and not on length o r age
Stages of prenatal development