Human Embryology Timeline

Human Embryology

Primordial Germ Cells form @ 3wks

PGCs migrate to genital ridge while

undergoing many mitotic divisions

Spermatogenesis

Spermatogonial Stem Cells

Oogenesis

Meiosis I

(Arrested at Prophase)

Puberty!

Meiosis I

Secondary Spermatocytes

Meiosis II

Spermatids

64 day turnover

Spermiogenesis

(MI Prophase) Primary oocytes

Leutenizing Hormone

Meiosis I

Secondary oocytes

+

first polar body

Meiosis II

(Arrested at Metaphase)

Ovulation

Capacitation

Fertilization

(MII Metaphase) Secondary Oocyte

Meiosis II

Ootid

+

Second Polar Body

Zygote

Implantation

Formation of a streak along midline of epiblast (upper layer of embryonic disc)

"finger in chocolate cake" analogy

Starts @ caudal end and elongates cranially

Neural Tube Formation

Day 17

Secondary Neural Tube

Spinal Cord

Brain

Secondary Brain Vesicles

Wk 5

Region-specific Migration

3 Axes of Development

Neural Crest

Formation

Cardiac

Boundary between neural plate and non-neural ectoderm

Cranial

Vagal & Sacral

Trunk

A subset of vagal neural crest – somites 1-3

Differentiation:

• Melanocytes, neurons, cartilage, connective tissue
• Migrate to outflow tract of heart (truncus arteriosus) and differentiates to form septum (separates pulmonary artery from aorta)
• Also forms smooth muscle of arteries from heart

Developmental errors

• Failure to septate congenital heart defects (clinical correlation with parathyroid conditions)
• Aortic arch artery defects

Migrate dorsolaterally to produce craniofacial mesenchyme

• Melanocytes
• craniofacial cartilage and bone
• connective tissue
• cranial ganglia

From rhombomeres, migrate into branchial (pharyngeal) arches

• Thymus
• tooth primordial
• some ear and jaw bones

Vagal – adjacent to somites 1-7

Sacral – posterior to somite 28

Differentiates into enteric ganglia of the gut

• Hirschprung disease – lack of enteric neurons in distal colon, due to migration/differentiation failure

Early pathway: Ventrolaterally through the anterior part of the sclerotome

• Dorsal root ganglia
• Sympathetic ganglia
• Adrenal medulla

Later pathway: Dorsolaterally adjacent to epidermis

• Melanocytes

2 pathways have different signals along path lead to different cell types

Somite Formation

Somitomere formation

Day 18-30

Cranial to caudal

Ribs

Somite formation

Day 20

Costal Processes

Day 45

Day 40

Day 35

Sterna bars connect 7 upper ribs ventrally. Ribs fuse cranialcaudal to form sternum

Costovertebral joint between vertebra and rib forms

Costal processes elongate to form ribs

Laeral mesenchymal condensation from vertebral arches of neck and trunk

Begins with somitomere 8

Somite migration

Begining at somite 6, single epithelial layer migrates to form:

• Sclerotome
• Myotome
• Dermatome

Gastrulation

2-layer embryo converts into 3-layer embryo

Vertebral Column

Primitive Streak (wk2-wk4)

Vertebral Body

Week 4

Portion of vertebral column formed by ventral sclerotome surrounding notochord

Begins at somite 6, progresses in cranial to caudal direction

Muscles

Myotome Differentiation into 2 cell types

Vertebral Arches

Day 16-wk4: Mesoderm

Definitive Endoderm

Day 14-15

• Epimere – deep muscles of back
• Hypomere – intercostals/abdomen muscles

Same time as Vertebral body

Vertebral column surrounding neural tube dorsally, formed from dorsal sclerotome

Stimulated by Neural Tube

Ingressing cells begin to fill space between epiderm and endoderm to form mesoderm

Axial Mesoderm -> Notochord

Paraxial Mesoderm -> Somites

Cleavage

First cells ingress through streak via epithelial to mesenchymal transition and displace hypoblast to form definitive endoderm

Myotubules – long, multinucleated muscle cells, formed from fusion of myoblasts

Myoblast – muscle stem cells

Resegmentation of Sclerotome

Invertebral Discs

First 3 Divisions

Compaction

Day 3

Hatching

Notochord

First cell differentiation event

Embryo enters "morula" stage

Zona Pellucida degenerates

Blastocyst is free floating in uterus

Sclerotome splits into cranial and caudal segments to make room for spinal nerves to grow from NT

Fuse at other end, so that sclerotome are offset from myotome and dermatome – sclerotome lie “intersegmentally” while somites lie segmentally

Sclerotome cells in segmental position surround notochord between vertebral bodies to form annulus fibrosus of intervertebral discs

Notochord process forms under ectoderm, via ingression

Extends from primitive pit to cranial end of embryo until prechordal plate

Formation of Blastocyst

Day 5

30 hrs after fertilization

In fallopian tube

Cells surrounded by zona pellucida

First divisions result in no overall size change

Cells=blastomeres, still totipotent

Oogonia

(mitotic proliferation)

PGCs

Primary oocytes

Allantois - Day 16

(Egg production)

Outpocketing on caudal wall of yolk sac, into connecting stalk

Reservoir for embryonic urine; respiratory function

Site of first blood cell formation (3-5 weeks)

Cells separate into:

- Inner Cell Mass

- Trophectoderm (trophoblasts)

Blastocoele formation - tight junctions form between outer cells, fluid is pumped in

Week 4

Week 6

Week 3

Week 2

Week 5

Week 1

Spermatids

Spermatozoa

Spermatogonia

(Sperm production)

Primary Spermatocytes

Spermatogonial stem cells

PGCs

In seminiferous tubules of testis

Primary Brain Vesicles

Wk 4

Neurulation

~6 days

Embryo implants into endometrial epithelium of upper posterior uterine wall

Ventricular Zone: site of cell differentiation and mitosis

Segmentation of Hindbrain - Rhombomere formation

Week 4-5

Amnion

Embryonic Disc

Day 24

Formation of neuroblasts

Day 9

Amniotic cavity forms between trophoblast and epiblast

Amnion - surrounds cavity, cells derived from epiblast

Formation of ependymal cells (secretory)

• In fully differentiated spinal cord, ventricular zone becomes Ependymal zone

Formation of glioblasts

Intermediate Zone (becomes gray matter)

ICM differentiates into:

-Epiblast - will give rise to embryonic tissue layers

-Hypoblast - becomes parietal endoderm and ultimately the yolk sacs

Extra-embryonic Mesoderm

Extra-embryonic Coelom

Houses neuronal cell bodies. Neuroblasts and glioblasts migrate here after differentiating in ventricular zone

Neural Folds & Neural Groove

Day 22

Sulcus Limitans

Wk 4

Neural Plate Extension

Day 18-22

Marginal Zone (becomes white matter)

Day 13

Fluid-filled cavity derived from fusion of cavities that develop in extraembryonic mesoderm

Day 9

Loose connective layer that surrounds amnion & primary yolk sac

Tissue will become part of chorion

Internal longitudinal groove in lateral wall

Separates Alar Plate from Basal Plate

Neural processes (axons, dendrites) and glial cells (myelin sheath)

Neural groove forms at midline, and neural folds are elevated on either side

Begins at cervical level, extends in both directions

Thickening of ectoderm

Columnar pseudostratified neuroepithelial cells

Extends cranial to caudal

Trophopblast Differentiation

Exocoelomic Cavity

Closing of Neural Tube

Day 22-26

Cavitation

Syncytiotrophoblasts - between embryo and mother, future placenta

Cytotrophoblast - surrounds blastocoele

Day 24

Cranial neuropore closes

Day 26

Caudal neuropore closes

Apposition and fusion of neural folds at dorsal midline

Neural canal = hollow space

~ 8 days

Wk 5 - Solid tube formation from caudal eminence

Wks 6-7

Cavitation

Wk 8

Fuses with neural tube

Day 8

Derived from blastocoelomic cavity

Exocoelomic membrane derived from parietal endoderm (hypoblasts)

Will become primary yolk sac

Limb Development

Decidual Response

Limb Bud Formation

Transformation of endometrium to decidua

• Decidua Basalis
• Decidua Capsularis
• Decidua Parietalis

Proximal-Distal

Local proliferation of mesenchymal cells in somatic layer of lateral plate mesoderm

• Upper limb buds – day 26 @ lower cervical region
• Lower limb buds – day 28 @ lower lumbar region

Anterior-Posterior

10-12 wks: CVS

Lacunae

Day 10

Apical Ectodermal Ridge (AER): thickening of ectoderm at apex of limb bud

• Induced when mesenchymal cells from lateral plate mesoderm migrate into limb field and secrete FGF10

Progress zone: region 200µm below AER

Major signaling molecules:

• FGF8 from AER
• FGF10 from mesenchyme

Progress Zone model vs. Prespecification model

Zone of Polarizing Activity (ZPA): block of mesoderm near posterior of junction of early limb bud and body wall that controls polarity of limb

Determines digit # & type

Major signaling molecule: SHH

• Secreted by ZPA

Dorsal-Ventral

Cavities in syncytiotrophoblasts filled with maternal blood

Major signaling molecule: Wnt7

• Expressed in dorsal ectoderm

Chorion

Day 14

Cytotrophoblast produces extensions into sycytiotrophoblast

Extra-embryonic mesoderm + Trophoblasts

Closing Plug

~Day 10

Placenta Development