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Embryology overview C. Riedinger                                                     1


                   Overview of what becomes what.

               Epiblast      Ectoderm
                                    Mesoderm
Embryoblast

               Hypoblast  Endoderm


Ectoderm
   -   Overall : epidermis, nervous system
   -   neural crest cells      glial and schwann cells
                               melanocytes
                               parts of meninges
                               parts of teeth
                               dorsal root, cranial, enteric, autonomic ganglia
                               connective tissue of face
                               bones of skull
                               adrenal medulla
   -   neural tube             brain + spinal cord

Mesoderm
   -   overall: skeletal, muscle, connective
   -   axial                   notochord  nucleus pulposus of vertebrae
   -   paraxial                somites       myotome, scleratome, dermatome
   -   intermediate            urogenital
   -   lateral plate (continuous with extra-embryonic mesoderm of
       amniotic cavity         parietal/somatic layer
       and yolk sac            visceral/splanchnic layer)
                               blood, peritoneum
                               intraembryonic coelum  pericardial, pleural and
                                                           peritoneal cavities

Endoderm
   -   overall:  gut tube, lining of GI tract and respiratory system (epithelium)
   -   pharyngeal arches
   -   thyroid gland (from foramen caecum)
   -   lung           (from respiratory diverticulum in foregut)
   -   liver          (hepatic diverticulum in duodenum)
   -   pancreas
   -   foregut:       bucopharyngeal membrane to midgut
   -   midgut:        foregut to hindgut, initially connected to yolk sac
   -   hindgut:       midgut to cloacal membrane, connecting stalk
                      (later to urogenital openings, allantois= “überhindgut”)
   -   parenchymal cells of liver, pancreas, parathyroid

Yolk sack  vitelline duct  meckel’s diverticulum (if not obliterated)
Embryology overview C. Riedinger                                                       2


Pharyngeal arches
       Pharyngeal          Pharyngeal          Pharyngeal             Pharyngeal
       arches              cartilages          pouches (inside)       clefts (outside)
  1    Vc:                 Aliphenoid          Tympanic cavity        External
       Mastication         malleolus incus     Eustachian tube        auditory
       MATT                Meckel’s                                   meatus
                           cartilage
  2    VII:                Stapes              Palatine tonsils
       facial expression   styloid process
       POSS                stylohyoid
                           ligament                                   Cervical sinus
                           lesser cornu of                            (obliterated)
                           hyoid
  3    XI:                 Greater cornu of    Inferior parathyroid
       stylopharyngeus     hyoid               thymus
                           body of hyoid
  4    Sup. laryngeal:     Thyroid cartilage   Superior
       cricothyroid        cricoid cartilage   parathyroid
       Middle + inferior   (could also be 6)   ultimo-branchial
       constrictor                             body (parafollicular
                                               calcitonin-
                                               producing cells)
  6    Recurrent
       laryngeal:
       larynx


Cross-talk between epithelium (endoderm) and mesenchyme
(mesoderm)
   -   mesenchyme = undifferentiated loose connective tissue derived mainly from
       mesoderm (some from neural crest cells though which are ectodermal)
   -   parenchyma = functional parts of an organ in the body
   -   stroma = structural tissue (connective, supportive)
   -   differentiation of endodermal epithelium dictated by signals from
       mesoderm (mesenchyme)
   -   stomach:       gastric glands
   -   intestines:    villi
   -   liver:         hepatic cords
   -   pancreas:
   -   lung:          branching morphogenesis
       branching (in bronchi) or inhibition of branching (trachea)
   -   kidney:        dichotomous branching
       ureteric bud induces mesoderm to become metanephric blastema
       /mesenchyme, which in turn induces further buds
Embryology overview C. Riedinger                                                 3


Endodermal derivatives
Lung
  - lung diverticulum (from gut endoderm) grows into splanchnopleuric/visceral
     mesoderm
  - branching morphogenesis: guided by FGF10, antagonist: sonic hedgehog
  - stages of lung growth: embryonic, pseudoglandular, canalicular, sacuular,
     alveolar

Stomach
   - thickening of foregut tube (differential growth)
            more on left  greater curvature
            less on right  lesser curvature
   - 90* clockwise rotation so that:
            left vagus       ant
            right            post
            ventral mesentery  right               lesser omentum
            dorsal mesentery         left          greater omentum
   - pylorus rises, this makes duodenum C-shaped
   - duodenum is half foregut half midgut

Liver
   - diverticulum from duodenal endoderm
   - pushes into septum transversum  ventral mesentery
   - gall bladder = ventral outpouching
   -
Pancreas
   - outgrowth of hepatic diverticulum
   - dorsal bud  accessory pancreatic duct / minor papilla
   - ventral bud  uncinate process, manjor papilla along with bile

Small intestine
  - rapid enlongation of midgut causes physiological umbilical hernia
  - 1* rotation, then another 90*, another 180*, all anticlockwise

Bladder
   - at cloacal membrane (no mesoderm) urogenital septum grows in to divide
      hindgut from allantois
   - urogenital septum  perineum (?)
   - widening of gut on allantoic side = urogenital sinus  bladder, urethra
      male: only prostatic and membranous urethra
      female: entire urethra
   - allantois  urachus  median umbilical ligament
Embryology overview C. Riedinger                                                  4


Mesodermal derivatives

Development of heart
   ♥ from angiogenic cell clusters in extra-embryonic mesoderm
   ♥ Two heart tubes form single tube during folding

   ♥   Truncus arteriosus           spiral septum  aorta + pulmonary trunk
   ♥   Bulboventricular groove
   ♥   Bulbis cordis                   conus cordis  RV / infundibulum
   ♥   Ventricle                       LV (trabeculated part)
   ♥   Atrioventricular groove         atrioventricular valves
                                       endocard. cushions sept. intermedium
       (septum intermedium between right and left AV canal)
       spiral septum eventually fuses with septum intermedium and muscular
       ventricular septum
   ♥   Atrium                                 auricles
   ♥   Sinus venosus (right sinus horn)  RA
   ♥   Left sinus horn                        coronary sinus
   ♥   Septum primum has osteum primum (which closes) and then osteum
       secundum, septum
   ♥   Right/left directionality determined by nodal gene

Fetal circulation:
   ♥ 3 shunts:
            o ductus venosus: closure within 5 days
            o foramen ovale
            o ductus arteriosus: closure within 10 days
   ♥ changes at birth:
            o lungs inflate, blood enters them and returns to the LA
            o p in LA > p in RA
            o foramen ovale shuts
            o prostaglandin levels decrease as no more flow from umbilical vein
   ♥ umbilical vein            ligamentum teres
   ♥ ductus venosus            ligamentum venosum
   ♥ foramen ovale             fossa ovalis
   ♥ ductus arteriosus         ligamentum arteriosum (left recurrent laryngeal
        winds around it)

Blood vessels:
   - vasculogenesis:        differentiation from within a cell mass
   - angiogenesis:          invasion of tissue from existing blood vessels
Embryology overview C. Riedinger                                              5


Septum transversum
   - thickened sheet of mesoderm between cardiogenic area and cranial margin of
      disc, later caudal and anterior to gut tube
   - septum transversum  central tendon of diaphragm
   - septum transversum also makes VENTRAL MESENTERY for caudal portion
      of foregut: liver, stomach, spleen
   - complete diaphragm develops from:
          o septum transversum
          o somatic mesoderm from body wall
          o mesentery of oesophagus
          o pleuroperitoneal membrane
          o myoblasts from cervical somites

Kidney
   - from intra-embryonic intermediate mesoderm
   - nephric part or urogenital ridge
   - pronephros             regresses early, non-functional
   - mesonephros            functional, regresses
   - metanephros            definite kidney
   - duct from pronephros through mesonephros to urogenital sinus = mesonephric
      duct (Wolffian duct)
   - mesonephric duct outpouching/metanephric diverticulum
       ureteric bud  metanephros
Embryology overview C. Riedinger                                                    6


Urogenital system
   - same origin as kidney, from from intra-embryonic intermediate mesoderm
   - gonadal part of urogenital ridge
   - migrating primordial germ cells enter and induce sex-specific differentiation =
      end of indifferent stage (germ cells originate from epiblast?)
      germ cells  spermatogonia / oocytes
   - SRY (XY gene product), SOX9 crucial for development of testes

male:
   - mesonephric duct                 vas deferens
                                      epididymis
                                      seminal vesicle
   -   paramesonephric duct           regresses to prostratic utricle, appendix of
                                     the testes, ejaculatory duct
   -   mesonephric mesenchyme  Leydig cells (make androgens!)
   -   making testosterone requires 5-alpha reductase
   -   sex cords                      sertoli cells (Muellerian inhibitory substance
                                     to suppress formation of femal genitalia!) +
                                     seminiferous tubules (spermatogenesis)
   -   gubernaculum guides descent of testes          gubernaculum
                                                      scrotal ligament
   -   genital tubercle / urogenital folds            penis
                                                      corpora cavernosa
                                                      corpus spongiosum
   -   labioscrotal swellings /folds                  scrotum


female:
   - mesonephric duct                 regresses to Gartner’s cyst in wall of vagina
   - paramesonephric duct             fallopian tubes
                                      uterus
                                      top of vagina
       (inf end of vagina develops from urogenital sinus (sinovaginal bulb))
   -   mesonephric mesenchyme  thecal cells (make corpuls luteum to make
                                     progesterone but also androgens)
   -   sex cords break up and condense around germ cells  primary follicles
   -   gubernaculum                   round ligament of ovary and uterus
   -   genital tubercle               clitoris
                                      corpus cavernosa
                                      bulbospongiosum
   -   urethral folds                 labia minora
   -   labioscrotal swellings         labia majora

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Embryology Overview

  • 1. Embryology overview C. Riedinger 1 Overview of what becomes what.  Epiblast  Ectoderm  Mesoderm Embryoblast  Hypoblast  Endoderm Ectoderm - Overall : epidermis, nervous system - neural crest cells  glial and schwann cells  melanocytes  parts of meninges  parts of teeth  dorsal root, cranial, enteric, autonomic ganglia  connective tissue of face  bones of skull  adrenal medulla - neural tube  brain + spinal cord Mesoderm - overall: skeletal, muscle, connective - axial  notochord  nucleus pulposus of vertebrae - paraxial  somites  myotome, scleratome, dermatome - intermediate  urogenital - lateral plate (continuous with extra-embryonic mesoderm of amniotic cavity  parietal/somatic layer and yolk sac  visceral/splanchnic layer)  blood, peritoneum  intraembryonic coelum  pericardial, pleural and peritoneal cavities Endoderm - overall:  gut tube, lining of GI tract and respiratory system (epithelium) - pharyngeal arches - thyroid gland (from foramen caecum) - lung (from respiratory diverticulum in foregut) - liver (hepatic diverticulum in duodenum) - pancreas - foregut: bucopharyngeal membrane to midgut - midgut: foregut to hindgut, initially connected to yolk sac - hindgut: midgut to cloacal membrane, connecting stalk (later to urogenital openings, allantois= “überhindgut”) - parenchymal cells of liver, pancreas, parathyroid Yolk sack  vitelline duct  meckel’s diverticulum (if not obliterated)
  • 2. Embryology overview C. Riedinger 2 Pharyngeal arches Pharyngeal Pharyngeal Pharyngeal Pharyngeal arches cartilages pouches (inside) clefts (outside) 1 Vc: Aliphenoid Tympanic cavity External Mastication malleolus incus Eustachian tube auditory MATT Meckel’s meatus cartilage 2 VII: Stapes Palatine tonsils facial expression styloid process POSS stylohyoid ligament Cervical sinus lesser cornu of (obliterated) hyoid 3 XI: Greater cornu of Inferior parathyroid stylopharyngeus hyoid thymus body of hyoid 4 Sup. laryngeal: Thyroid cartilage Superior cricothyroid cricoid cartilage parathyroid Middle + inferior (could also be 6) ultimo-branchial constrictor body (parafollicular calcitonin- producing cells) 6 Recurrent laryngeal: larynx Cross-talk between epithelium (endoderm) and mesenchyme (mesoderm) - mesenchyme = undifferentiated loose connective tissue derived mainly from mesoderm (some from neural crest cells though which are ectodermal) - parenchyma = functional parts of an organ in the body - stroma = structural tissue (connective, supportive) - differentiation of endodermal epithelium dictated by signals from mesoderm (mesenchyme) - stomach: gastric glands - intestines: villi - liver: hepatic cords - pancreas: - lung: branching morphogenesis branching (in bronchi) or inhibition of branching (trachea) - kidney: dichotomous branching ureteric bud induces mesoderm to become metanephric blastema /mesenchyme, which in turn induces further buds
  • 3. Embryology overview C. Riedinger 3 Endodermal derivatives Lung - lung diverticulum (from gut endoderm) grows into splanchnopleuric/visceral mesoderm - branching morphogenesis: guided by FGF10, antagonist: sonic hedgehog - stages of lung growth: embryonic, pseudoglandular, canalicular, sacuular, alveolar Stomach - thickening of foregut tube (differential growth) more on left  greater curvature less on right  lesser curvature - 90* clockwise rotation so that: left vagus  ant right  post ventral mesentery  right  lesser omentum dorsal mesentery  left  greater omentum - pylorus rises, this makes duodenum C-shaped - duodenum is half foregut half midgut Liver - diverticulum from duodenal endoderm - pushes into septum transversum  ventral mesentery - gall bladder = ventral outpouching - Pancreas - outgrowth of hepatic diverticulum - dorsal bud  accessory pancreatic duct / minor papilla - ventral bud  uncinate process, manjor papilla along with bile Small intestine - rapid enlongation of midgut causes physiological umbilical hernia - 1* rotation, then another 90*, another 180*, all anticlockwise Bladder - at cloacal membrane (no mesoderm) urogenital septum grows in to divide hindgut from allantois - urogenital septum  perineum (?) - widening of gut on allantoic side = urogenital sinus  bladder, urethra male: only prostatic and membranous urethra female: entire urethra - allantois  urachus  median umbilical ligament
  • 4. Embryology overview C. Riedinger 4 Mesodermal derivatives Development of heart ♥ from angiogenic cell clusters in extra-embryonic mesoderm ♥ Two heart tubes form single tube during folding ♥ Truncus arteriosus  spiral septum  aorta + pulmonary trunk ♥ Bulboventricular groove ♥ Bulbis cordis  conus cordis  RV / infundibulum ♥ Ventricle  LV (trabeculated part) ♥ Atrioventricular groove  atrioventricular valves  endocard. cushions sept. intermedium (septum intermedium between right and left AV canal) spiral septum eventually fuses with septum intermedium and muscular ventricular septum ♥ Atrium  auricles ♥ Sinus venosus (right sinus horn)  RA ♥ Left sinus horn  coronary sinus ♥ Septum primum has osteum primum (which closes) and then osteum secundum, septum ♥ Right/left directionality determined by nodal gene Fetal circulation: ♥ 3 shunts: o ductus venosus: closure within 5 days o foramen ovale o ductus arteriosus: closure within 10 days ♥ changes at birth: o lungs inflate, blood enters them and returns to the LA o p in LA > p in RA o foramen ovale shuts o prostaglandin levels decrease as no more flow from umbilical vein ♥ umbilical vein  ligamentum teres ♥ ductus venosus  ligamentum venosum ♥ foramen ovale  fossa ovalis ♥ ductus arteriosus  ligamentum arteriosum (left recurrent laryngeal winds around it) Blood vessels: - vasculogenesis: differentiation from within a cell mass - angiogenesis: invasion of tissue from existing blood vessels
  • 5. Embryology overview C. Riedinger 5 Septum transversum - thickened sheet of mesoderm between cardiogenic area and cranial margin of disc, later caudal and anterior to gut tube - septum transversum  central tendon of diaphragm - septum transversum also makes VENTRAL MESENTERY for caudal portion of foregut: liver, stomach, spleen - complete diaphragm develops from: o septum transversum o somatic mesoderm from body wall o mesentery of oesophagus o pleuroperitoneal membrane o myoblasts from cervical somites Kidney - from intra-embryonic intermediate mesoderm - nephric part or urogenital ridge - pronephros  regresses early, non-functional - mesonephros  functional, regresses - metanephros  definite kidney - duct from pronephros through mesonephros to urogenital sinus = mesonephric duct (Wolffian duct) - mesonephric duct outpouching/metanephric diverticulum  ureteric bud  metanephros
  • 6. Embryology overview C. Riedinger 6 Urogenital system - same origin as kidney, from from intra-embryonic intermediate mesoderm - gonadal part of urogenital ridge - migrating primordial germ cells enter and induce sex-specific differentiation = end of indifferent stage (germ cells originate from epiblast?) germ cells  spermatogonia / oocytes - SRY (XY gene product), SOX9 crucial for development of testes male: - mesonephric duct  vas deferens  epididymis  seminal vesicle - paramesonephric duct  regresses to prostratic utricle, appendix of the testes, ejaculatory duct - mesonephric mesenchyme  Leydig cells (make androgens!) - making testosterone requires 5-alpha reductase - sex cords  sertoli cells (Muellerian inhibitory substance to suppress formation of femal genitalia!) + seminiferous tubules (spermatogenesis) - gubernaculum guides descent of testes  gubernaculum  scrotal ligament - genital tubercle / urogenital folds  penis  corpora cavernosa  corpus spongiosum - labioscrotal swellings /folds  scrotum female: - mesonephric duct  regresses to Gartner’s cyst in wall of vagina - paramesonephric duct  fallopian tubes  uterus  top of vagina (inf end of vagina develops from urogenital sinus (sinovaginal bulb)) - mesonephric mesenchyme  thecal cells (make corpuls luteum to make progesterone but also androgens) - sex cords break up and condense around germ cells  primary follicles - gubernaculum  round ligament of ovary and uterus - genital tubercle  clitoris  corpus cavernosa  bulbospongiosum - urethral folds  labia minora - labioscrotal swellings  labia majora