UNSW Embryology

Day

Menstrual cycle

Event

1

Menstrual Phase

Menstrual cycle changes: Uterine endometrium (loss), Ovary (Follicle Development)

2

3

4

5

Proliferative Phase

Menstrual cycle changes: Uterine endometrium (proliferation), Ovary (Follicle Development)

6

7

Day

Event

8

Proliferative Phase

9

Mid proliferative

10

11

12

13

Late Proliferative

14

Ovulation

Capacitation

Day

Stage

Event

1

Secretory Phase
Stage 1

Fertilization, Secretory Phase

2

Stage 2

Morula, Blastula

3

4

Stage 3

Blastocyst Hatching (zona pellucida lost)

5

Blastocyst (free floating)

6

Stage 4

Adplantation

7

Stage 5

Day

Stage

Event

8

Implantation

9

10

11

12

13

Stage 6

14

Day

Stage

Event

15

16

Stage 7

17

18

Stage 8

Neural – neurogenesis, neural groove and folds are first seen

19

20

Stage 9

Musculoskeletal – somitogenesis, first somites form and continue to be added in sequence caudally

Neural – the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open

Neural Crest – mesencephalic neural crest is visible (PMID: 17848161)

21

Heart – cardiogenesis, week 3 begins as paired heart tubes.

Day

Stage

Event

22

Stage 10

Neural Crest – differentiation at spinal cord level from day 22 until day 26

Neural – neural folds begin to fuse near the junction between brain and spinal cord, when Neural Crest cells are arising mainly from the neural ectoderm

Neural Crest – trigeminal, facial, and postotic ganglia components visible (PMID: 17848161)

Neural Crest – migration of vagal level neural crest cells begins (7-10 somite stage)

Brain – rostral neural tube forms 3 primary brain vesicles (week 4)

Respire – Week 4 - laryngotracheal groove forms on floor foregut.

23

Heart – begins to beat in Humans by day 22-23, first functioning embryonic organ formed.

24

Stage 11

Thyroid – thyroid median endodermal thickening in the floor of pharynx

Neural – rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in two areas simultaneously. The two lips, however, behave differently.

Optic ventricle appears

25

Stage 12

Pituitary Week 4 – hypophysial pouch, Rathke’s pouch, diverticulum from roof

GIT - Liver – septum transversum forming liver stroma and hepatic diverticulum forming hepatic trabeculae (PMID: 9407542)

Neural – caudal neuropore takes a day to close (closure is approximately at future somitic pair 31/sacral vertebra 2)

Neural – secondary neurulation begins

Neural Crest – cardiac crest, neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there the truncus arteriosus (PMID: 17848161)

Neural Crest – vagal neural crest enter the foregut (20-25 somite stage)

26

27

28

Stage 13

Neural – the neural tube is normally completely closed, ventricular system now separated from amniotic fluid. Neural crest at spinal level is segregating, and spinal ganglia are in series with the somites. Spinal cord ventral roots beginning to develop. (PMID: 3354839)

telencephalon cavity appears

GIT - Liver – epithelial cord proliferation enmeshing stromal capillaries (PMID: 9407542)

Sense - Smell – Crest comes from the nasal plates (PMID: 15604533)

Skin – 4 weeks - simple ectoderm epithelium over mesenchyme

Skin – 1-3 months ectoderm- germinative (basal) cell repeated division of generates stratified epithelium; mesoderm- differentiates into connective tissue and blood vessels

Day

Stage

Event

29

Pituitary Week 5 – elongation, contacts infundibulum, diverticulum of diencephalon

Heart – Week 5 septation starts, atrial and ventricular

Respire – Week 5 - left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity)

Respire – Week 5-17 lung histology - pseudoglandular

Sense - Hearing – Week 5 - cochlear part of otic vesicle elongates (humans 2.5 turns)

30

31

32

Stage 14

Ectoderm - sensory placodes, lens pit, otocyst, nasal placode, primary/secondary vesicles, fourth ventricle of brain

Mesoderm - continued segmentation of paraxial mesoderm (somite pairs), heart prominence

Head - 1st, 2nd and 3rd pharyngeal arch, forebrain, site of lens placode, site of otic placode, stomodeum

Body - heart, liver, umbilical cord, mesonephric ridge visible externally as bulges.

Limb - upper and lower limb buds growing

Neural – first appearance of the future cerebral hemispheres. Cerebellar plate differentiated to an intermediate layer, and future rhombic lip identifiable (PMID: 3377191)

GIT - Liver – hepatic gland and its vascular channels enlarge, hematopoietic function appears (PMID: 9407542)

33

Stage 15

Neural – cranial nerves (except olfactory and optic) are identifiable in more advanced embryos (PMID: 3213956)

34

35

Eye - 35 to 37 days retinal pigment present

Day

Stage

Event

36

Pituitary Week 6 - connecting stalk between pouch and oral cavity degenerates

Parathyroid Week 6 - diverticulum elongate, hollow then solid, dorsal cell proliferation

Thymus Week 6 - diverticulum elongate, hollow then solid, ventral cell proliferation

Adrenal Week 6 – fetal cortex forms from mesothelium adjacent to dorsal mesentery, medulla neural crest cells from adjacent sympathetic ganglia

Respire – Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes

Tongue – Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes gustatory papilla, caudal midline near the foramen caecum (week 6 to 7 - nerve fibers approach the lingual epithelium)

37

Stage 16

Neural first parasympathetic ganglia, submandibular and ciliary, are identifiable (PMID: 2751117)

Limbs – upper limb bud nerves median nerve, radial nerve and ulnar nerve entered into hand plate, myoblasts spindle shaped and oriented parallel to limb bud axis.

Heart – outflow tract elliptical configuration with four cushions, the two larger fusing at this stage. Semilunar valve leaflets form at the downstream end of the cushions

Head – lip and palate components of the upper lip, medial nasal prominence and maxillary process present, median palatine process appears.

38

39

40

41

Stage 17

Neural – telencephalon areas of the future archicortex, paleocortex, and neocortex, visible. Beginning of future choroid plexus (PMID: 2802187)

Sense - Smell – olfactory nerve fibres enter the brain (PMID: 15604533)

Neural – primordium of the epidural space appears first on the ventral part of the vertebral canal and develops rostro-caudally (PMID: 15478101)

42

Heart – separation of common cardiac outflow (aortic arch and pulmonary aorta)

Day

Stage

Event

43

Pancreas Week 7 to 20 – pancreatic hormones secretion increases, small amount maternal insulin

Respire – Week 7 - enlargement of liver stops descent of heart and lungs

44

Stage 18

Limb – bones form by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5-12).

Sense - Smell – vomeronasal fibres and nervus terminalis (PMID: 15604533)

GIT - Liver – obturation due to epithelial proliferation, bile ducts became reorganized, continuity between liver cells and gut (PMID: 9407542)

Neural – duramater appears (PMID: 15478101)

45

GIT - Liver (stage 18 to 23) – biliary ductules developed in periportal connective tissue

produces ductal plates that receive biliary capillaries (PMID: 9407542)

46

47

48

Stage 19

Neural – accessory olivary nucleus appears (PMID: 2268071)

49

Day

Stage

Event

50

Stage 20

Head – scalp vascular plexus visible

Limb – upper limbs begin to rotate ventrally

Neural – amygdaloid body has at least four individual nuclei (PMID: 2268071)

oculomotor nerve shows a dorsolateral and a ventromedial portion

rhombic lip (rhombencephalon) formation of the cerebellum (intermediate layer) and of the cochlear nuclei

cerebellum cell layer (future Purkinje cells) develops

choroid plexuses of the fourth and lateral ventricles

51

Gastrointestinal Tract – anal membrane perforates

52

Stage 21

Neural – cortical plate appears in the area of future insula (PMID: 2252222)

Limb – upper and lower limbs rotate

Intraembryonic Coelom – pericardioperitoneal canals close

53

54

Stage 22

Neural – neocortical fibres project to epithalamus, to dorsal thalamus, and to mesencephalon (PMID: 2252222)

Limb – fingers and toes lengthen

Sense - Smell – Stage 22 to early fetal period - migratory streams of neurons from the subventricular zone of the olfactory bulb towards the future claustrum (PMID: 15604533)

55

Genital 8 Weeks – Testis - mesenchyme, interstitial cells (of Leydig) secrete testosterone, androstenedione

Genital 8 to 12 Weeks - hCG stimulates testosterone production

Tongue – Week 8 - nerves penetrate epitheilai basal lamina and synapse with undifferentiated, elongated, epithelial cells (taste bud progenitor cell)

56

Stage 23

Stage 23 defines the end of the embryonic (organogenesis) period

Mesoderm – heart prominence, ossification continues

Head – nose, eye, external acoustic meatus, eyelids, external ears, rounded head

Body - straightening of trunk, heart, liver, umbilical cord, intestines herniated at umbilicus

Limb – upper limbs longer and bent at elbow, hands and feet turned inward, foot with separated digits, wrist, hand with separated digits

Extraembryonic Coelom – chorionic cavity is now lost by fusion with the expanding amniotic cavity

Neural – rhombencephalon, pyramidal decussation present, nuclei and tracts similar to those present in the newborn cerebellum present as only a plate connected to midbrain and hindbrain through fibre bundles (PMID: 2244584)

Axial Skeleton – vertebral column 33 or 34 cartilaginous vertebrae (20-33 mm in total length), vertebral pedicles, articular and transverse processes identifiable (no spinous processes) (PMID: 7216919)

GIT - Stomach - Week 8 - Gastrin containing cells in stomach antrum. Somatostatin cells in both the antrum and the fundus.

Day

Stage

Event

57

Sense - Hearing – Week 9 - mesenchyme surrounding membranous labrynth (otic capsule) chondrifies

Sense - Smell – Embryonic/Fetal transition - localized incomplete lamination of the olfactory bulb (PMID: 15604533)

58

59

60

61

62

63

Week 9 - CRL 43 mm, femur length 6 mm

9 weeks CRL 50 mm - genitalia in both sexes look identical (PMID: 17875485)

uterus - paramesonephric ducts come into apposition with the urorectal septum and begin to fuse

Day

Stage

Event

64

Gastrointestinal Tract – Week 10 intestines in abdomen

Pituitary – growth hormone and ACTH detectable

Pancreas – Week 10 glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins

Tongue – Week 10 shallow grooves above the taste bud primordium

GIT - Stomach - Week 10 - Glucagon containing cells in stomach fundus.

65

66

67

68

69

70

Week 10 - CRL 55 mm, femur length 9 mm, biparietal diameter 17 mm

Day

Stage

Event

71

Thyroid – colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis

GIT - Stomach - Week 11 - Serotonin containing cells in both the antrum and the fundus.

72

73

74

75

76

77

Week 11 - CRL 68 mm, femur length 12 mm, biparietal diameter 20 mm

Week

Stage

Event

12

Clinical second trimester

Week 12 - CRL 85 mm, femur length 15 mm, biparietal diameter 25 mm

Sense - Hearing – Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph

Genital – male and female external genital differences observable

Respire – Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant

Tongue – Week 12 - first differentiated epithelial cells (Type II and III)

female genital canal (80 days) formed with absorption of the median septum

13

Tongue – Week 12 to 13 - maximum synapses between cells and afferent nerve fibers

14

Tongue – Week 14 to 15 - taste pores develop, mucous

15

Pancreas – glucagon detectable in fetal plasma

16

14 cm

Sense - Hearing – Week 16-24 - Centres of ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.

Pituitary – adenohypophysis fully differentiated

Respire – Week 16 to 25 lung histology - canalicular

Skin – 4 months - basal cell- proliferation generates folds in basement membrane; neural crest cells- (melanocytes) migrate into epithelium; embryonic connective tissue- differentiates into dermis, a loose ct layer over a dense ct layer. Beneath the dense ct layer is another loose ct layer that will form the subcutaneous layer. Ectoderm contributes to nails, hair follictles and glands. Nails form as thickening of ectoderm epidermis at the tips of fingers and toes. These form germinative cells of nail field. Cords of these cells extend into mesoderm forming epithelial columns. These form hair follocles, sebaceous and sweat glands.

primary follicles begin to form in the ovary and are characterized by an oocyte

glandular urethra forms and skin folds present

17

18

Tongue – Week 18 - substance P detected in dermal papillae, not in taste bud primordia

Skin – vernix caseosa covers skin

Spleen - α-SMA-positive reticulum cells increase in number and begin to form a reticular framework. PMID: 1925578

19

20

Pituitary – week 20 to 24 – growth hormone levels peak, then decline

Skin – lanugo, skin hair

Skin – 5 months - Hair growth initiated at base of cord, lateral outgrowths form associated sebaceous glands; Other cords elongate and coil to form sweat glands; Cords in mammary region branch as they elongate to form mammary glands.

21

22

Neural – brain cortical sulcation - sylvian fissure, interhemispheric fissure, callosal sulcus, parietooccipital fissure, and hippocampic fissures present(PMID:11158907

Spleen - antigenic reticular framework diversity, T and B lymphocytes segregated in the framework PMID: 1925578

23

24

Respire – Week 24 to 40 lung histology - terminal sac

Earliest potential survival expected if born

ovarian follicles can consist of growing oocytes surrounded by several layers of granulosa cells

25

Respire – end month 6 alveolar cells type 2 appear and begin to secrete surfactant

Week

Stage

Event

Clinical third trimester

Sense - Hearing – 3rd Trimester - vibration acoustically of maternal abdominal wall induces startle respone in fetus.

27

28

Respire – Month 7 - respiratory bronchioles proliferate and end in alveolar ducts and sacs

29

30

Genital – male gonad (testes) descending

31

32

33

Neural – brain cortical sulcation - primary sulci present (PMID:11158907)

34

Neural – brain cortical sulcation - insular, cingular, and occipital secondary sulci present (PMID:11158907)

35

36

37

38

Birth

Clinical Week 40

Heart – pressure difference closes foramen ovale leaving a fossa ovalis

Thyroid – TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels

Adrenal - zona glomerulosa, zona fasiculata present

Week

Stage

Event

+2

+3

+4

+5

Year

Year1

Hearing - (6 months to 5 years) thalamocortical afferents to the deeper cortical layers mature and are the first source of input to the auditory cortex (PMID: 12018354)

Year 2

Year 3

Adrenal - Year 3 – zona reticularis present

4

5

Hearing - (5 to 12 years) commissural and association axons in the superficial cortical layers allows communication between subdivisions of the auditory cortex (PMID: 12018354)

37

38

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