Gestational Day GA Stage Event

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8 Proliferative Phase

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Fertilization Day Stage Event

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Day Stage Event

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18 Stage 8 neural neurogenesis, neural groove and folds are first seen

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20 Stage 9 Musculoskeletal somitogenesis, first somites form and continue to be added in sequence caudally (1 - 3 somite pairs). 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[1]

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 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[1] Neural Crest migration of vagal level neural crest cells begins (7-10 somite stage) neural rostral neural tube forms 3 primary brain vesicles (week 4) respiratory 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. ventricular Optic ventricle appears and the neural groove/tube space is initially filled with amniotic fluid.[2]

25 Stage 12 pituitary Week 4 hypophysial pouch, Rathke's pouch, diverticulum from roof liver septum transversum forming liver stroma and hepatic diverticulum forming hepatic trabeculae[3] neural caudal neuropore takes a day to close (closure is approximately at future somitic pair 31/sacral vertebra 2) neural secondary neurulation begins ventricular onset of the ventricular system and separates the ependymal from the amniotic fluid.[2] neural crest cardiac crest, neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there the truncus arteriosus[1] neural crest vagal neural crest enter the foregut (20-25 somite stage)

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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.[4] telencephalon cavity appears Neural - Vascular Development - hindbrain is supplied by two parallel neural arteries (or channels) that obtain their blood supply from carotid-vertebrobasilar anastomoses given by the pharyngeal arch arteries; trigeminal artery, the otic artery, hypoglossal artery, and the proatlantal artery.[5] liver epithelial cord proliferation enmeshing stromal capillaries[3] smell Crest comes from the nasal plates[6] integumentary 4 weeks - simple ectoderm epithelium over mesenchyme integumentary 1-3 months ectoderm- germinative (basal) cell repeated division of generates stratified epithelium; mesoderm- differentiates into connective tissue and blood vessels vision Optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lens placode.[7] Diaphragm - pleuroperitoneal fold (PPF) first discernible in human embryos (CRL 6mm).[8]

29 pituitary Week 5 elongation, contacts infundibulum, diverticulum of diencephalon heart Week 5 septation starts, atrial and ventricular respiratory Week 5 left and right lung buds push into the pericardioperitoneal canals (primordia of pleural cavity) Respiratory Week 5 to 17 lung histology - pseudoglandular hearing Week 5 cochlear part of otic vesicle elongates (humans 2.5 turns)

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33 Stage 15 neural cranial nerves (except olfactory and optic) are identifiable in more advanced embryos[12] Neural - Vascular Development - vertebral arteries form from transverse anastomoses between cervical intersegmental arteries, beginning with the proatlantal artery and proceeding downward to the 6th intersegmental artery,[5] vision lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.[7]

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35 vision 35 to 37 days retinal pigment present

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 respiratory Week 6 - descent of heart and lungs into thorax. Pleuroperitoneal foramen closes tongue Week 6 - 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[13] Neural - Vascular Development - development of the middle cerebral artery is first identified as small buds originating proximal to the anterior cerebral artery on the anterior division of the primitive internal carotid artery.[5] limb 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. Abdominal Wall muscle cell migration about 25% of the hemicircumference of the abdominal cavity, the lateral plate mesoderm has become more condensed and thicker in the area around the myoblasts.[9] 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. Eyelid prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.[7]

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41 Stage 17 neural telencephalon areas of the future archicortex, paleocortex, and neocortex, visible. Beginning of future choroid plexus [14] ventricular primordium of the epidural space appears first on the ventral part of the vertebral canal and develops rostro-caudally [15]

smell olfactory nerve fibres enter the brain [6]

Eyelid sulcus (groove) above and below eye deepen and eyelid folds develop (below first and then above) [7]

Diaphragm - pleuroperitoneal fold (PPF) no longer separated from the diaphragm (CRL 14mm) [8]

Abdominal Wall muscle cells now migrated approximately 50% of the distance to the ventral midline, inner and outer layers were not discernible yet.[9]

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 respiratory Week 7 - enlargement of liver stops descent of heart and lungs

44 Stage 18 limb bone forms by endochondrial ossification and throughout embryo replacement of cartilage with bone (week 5-12). neural smell vomeronasal fibres and nervus terminalis[6] liverobturation due to epithelial proliferation, bile ducts became reorganized, continuity between liver cells and gut[3] ventricular duramater appears and spaces surround the circumference of the spinal cord, which coalesce and contain many blood vessels.[15] Female uterus opening of the paramesonephric (Müllerian) duct to the coelomic cavity formed as an invagination of the coelomic epithelium[16] Abdominal Wall separation of the myoblasts into distinct inner and outer layers, with unidirectional orientation. Abdominal wall thicker in the region where secondary structures were forming compared with the primary body wall region, dorsally outermost layer of connective tissue approximately half of this thickness.[9]

45 liver (stage 18 to 23) biliary ductules developed in periportal connective tissue produces ductal plates that receive biliary capillaries[3]

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50 Stage 20 Head scalp vascular plexus visible limb upper limbs begin to rotate ventrally neural amygdaloid body has at least four individual nuclei[24] 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 Eyelid the inner canthus is established.[7]

51 gastrointestinal tract anal membrane perforates

52 Stage 21 neural cortical plate appears in the area of future insula[25] Neural - Vascular Development - formation of the anterior communicating artery.[5] limb upper and lower limbs rotate Intraembryonic Coelom pericardioperitoneal canals close Abdominal Wall Myoblasts have reached the ventral midline and myotubes were present and oriented uniformly within all muscle groups. The rectus abdominis formed distinct bundles of muscle. Connective tissue layers comprised the majority of the thickness of the abdominal wall, outermost layer of connective tissue accounted for the majority of this thickness.[9]

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54 Stage 22 neural neocortical fibres project to epithalamus, to dorsal thalamus, and to mesencephalon[25] limb fingers and toes lengthen smell Stage 22 to early fetal period - migratory streams of neurons from the subventricular zone of the olfactory bulb towards the future claustrum[6] Uterus Vagina fused duct (uterovaginal canal) bifurcated at the caudal portion at Carnegie stages 22 and 23[16]

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)[26]

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, 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[27] 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)[28] Abdominal Wall Rectus muscle forms 2 or 3 distinct layers with myotube orientation uniform in all muscles. The external oblique and internal oblique started to expand in thickness, transversus a thin layer of muscle.[9]

Week 8 Stomach Week 8 - Gastrin containing cells in stomach antrum. Somatostatin cells in both the antrum and the fundus. Genital - Female Development paired paramesonephric (Müllerian) ducts contact each other and are fused into a single tube that separates again and returns to the mesonephric (Wolffian) ducts. The paramesonephric ducts have not yet reached the urogenital sinus.[16]

57-63 Week 9 Beginning of Fetal Development

Historic Embryology In 1949 the embryologist George Streeter[29] used the replacement of cartilage within the humerus by bone marrow as an arbitrary definition of the embryo to fetus transition. "If the onset can be recognized in a given specimen, that specimen is straightway classed as a fetus."

CRL 43 mm, femur length 6 mm 9 weeks CRL 50 mm - genital genitalia in both sexes look identical[30] 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 Stomach Week 10 - Glucagon containing cells in stomach fundus. Nail Development fingernails appear outer ear Week 10 - Meatal plug extends in a disc-like fashion, the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. Proximal portion of the neck starts to be resorbed. inner ear Week 10 - neural-crest-derived melanocytes migrate into the cochlea. They penetrate the basement membrane of the lateral wall epithelium and develop into the intermediate cells of the stria vascularis.[31]

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

Day Stage Event neural - Cerebrum appearance of the first sulcus (week 11-15, GA 13-17 weeks)[32]

71 Thyroid colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis Stomach Week 11 - Serotonin containing cells in both the antrum and the fundus.

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