Embryo
Sperm hit membrane and trigger acrosome to breakdown and release hyaluronidase (breaks down junctions between radiate cells) and acrosin (break down the zona pellucida) 
Sperm Fusion (thought to be due to fertillin on sperm cell binds to integrins on the egg) to the Egg triggers a Calcium wave (occurs within a minute upto 15-20).
Cortical Reaction: Ca2+ activate cortical granules to release contents via exocytosis that inactivate Zona Pellucida (Z3 protein and partially cleave Z2) so no more sperm can bind. Prevents polyspermy
Secondary oocyte (egg) completes second meiotic division leads to formation of mature oocyte (ovum) forming 1 polar body and 1 female pronucleus
Sperm injected Nucleus, Tail, and other organelles into cytoplasm
Female and Male
DNA undergoes replication
Male and Female Pronuclei dissolve (46 total chromosomes) - spindle forms - chromosomes line up on metaphase plate
Zygote becomes 2-Cell embryo via cytokinesis. Each cell in the egg is called a blastomere. Cells are totipotent.
6-7 Hours
1 Minute
Each blastomere divides and you get 4 total. Cells are starting to flatten on each other.
8 rounded blastomeres, get smaller with every division.
Morula Formation 12 cells - 1 cell is inside. Outer cells are trophoblasts and inner cell is start of inner cell mass (ICM). They become what they will due to internal environment. Outer cells express Na+/K+ ATPase and begin to express adherens junctions, desmosomes, tight junctions which allow them to flatten. ICM cells are pluripotent.
Early Blastocyst. Pumps are forming cavity and cells are dividing. Blastocoel cavity is visible. First Stage with two cell types
3 Days
Late Blastocyst. Hatch from Zona Pellucida. It tumbles down the uterus to find a place to implant.
4.5 Days
Blastocyst attaches to the endometrium of uterus. Oriented so ICM area of the cell (embryonic pole) is nearest to the uterus. Trophoblast cells have Selectins which loosely bind to receptors on mucosa cells of the endometrium. followed by Trophoblasts expressing Integrins which provide a powerful attachment. Trophoblasts secrete hCG which gives feedback an supports survival of corpus luteum.
4.5 - 5 Days
Trophectoderm differentiates into cytotrophoblasts (cellular trophobalsts) and syncytiotrophoblast (synctial trophoblast), that have one membrane surrounding the whole embryo with multiple nuclei. Synctial trophoblast secretes matrix metallopeptidases (MMPs) to digest cell junctions of the endometrial epithelium until it reaches the decidua.
The embryo is fully into the uterine wall. Syncytiotrophoblast form trophoblastic lacuna (fluid filled). ICM becomes a bilaminar disc. Epiblast(columnar cells) form on side closest to synctiotrophoblast and the hypoblast(cuboidal cells) to the blastocoel cavity. These two layers form cavities: Epiblast (primary endoderm) forms the amniotic cavity and the hypoblast (primary/primitive endoderm) cells migrate around the inside of the blastocoel cavity on the cytotrophoblasts to begin forming the Heuser's membrane.
7 Days
Heuser's Membrane is complete and the cavity is now called the primary yolk sac. Synctiotrophoblast cells produce and secrete a digestive enzyme that allows them to digest arteriole and veniole capillaries which allows trophoblastic lacuna fill with mother's blood and bath the syncytiotrophoblast cells with nutrients. Cytotrophoblast cells are dividing. Heuser's membrane cells are secreting extraceullular matrix (ECM) materials and together is becoming the Extraembryonic reticulum. This is to provide space for extraembryonic mesoderm
9 Days
The Lacuna are still bathing. Extraembryonic mesoderm is formed from the epiblast. Extraembryonic mesoderm covers the entire interior of the embryo between it and the cytotrophoblast cells. The Heuser's membrane cells cannot secrete so the extraembryonic reticulum begins to break down
10 - 11 Days
Extraembryonic reticulum is gone and the cavity it left behind is called the Chorionic cavity. This cavity will expand over the next 8 months. Hypoblast (primary endoderm) cells begin to proliferate and migrate over inner surface of the extra embryonic mesoderm. Begins to form the definitive yolk sac and cleave off the primitive yolk sac.
12 Days
Primary yolk sac are pinched off and give rise to the definitive yolk sac which is enclosed by myoblast cells. Definitive yolk sac will help give rise to blood cell formation via an oxygen gradient set up. The extraembryonic mesodermal cells is where the blood cells are made (hematopoesis) and the hypoblast cells setup the oxygen gradient. Yolk sac stops growing by about week 4-5. Primary yolk sac dintegrates on opposite/abemryonic pole of the embryo.
12 - 13 Days
Bilaminar disc is formed and it is connected to the extraembryonic mesoderm via connecting stalk. You have Epiblast and Hypoblast (closest to the "middle").
Gastrulation Begins. Primitive streak forms on the epiblast (primary/primitive ectoderm) on the amniotic cavity side consisting of the primitive groove, node, and pit. Forms from caudally extending cranially. Cloacal Membrane (future anus) forms caudally from the streak. The buccopharyngeal membrane (future mouth) forms on the cranial end past the streak.
13 Days
Day 14
Day 14 - 15
Epiblast cells begin to ingress through the primitive streak and displaces the hypoblast cells. These cells become the definitive endoderm. The displaced hypoblast cells recede into the yolk sac.
Epiblast cells ingress through the primitive streak and node, after the definitive endoderm is formed, and fills in the space between the two in order to form the definitive mesoderm. These epiblast cells are mesenchymal (NOT cubodial or stratified)(does not make them mesoderm cells) cells as they move through the primitive streak. These cells can go through a cell cycle in 4.5 hours (fastest of any cell, ever). Movement pattern of epiblast cells through the primitive streak to become the mesoderm. Epiblast cells secrete hyaluronic acid to prevent these mesoderm cells from aggregating too soon. Fibronectin on the ectoderm helps the mesoderm cells "walk" via convergence and extension.
The precordal plate critical for forebrain formation) is formed from epiblast cells that came through the primitive node. The cells that come after this form the Notochord process as the primitive streak begins to regress in a caudal direction, which causes the notochord process to elongate cranially to caudally. The notochord process has a hole in the middle of it at this point.
Day 16
Notochord process will fuse with the underlying definitive endoderm, forming the notochordal plate. This allows the notochord cells to interact with the environment of the yolk sac.
To direct differentiation of the mesoderm. The primitive streak and node secrete SHH and FGF-8. Normally cilia on the ectoderm near the node help distribution it to the left axis.
Day 17
Notochord plate exists for 1-2 days and then it rises out of the endoderm. It is now called the definitive notochord and has no hole in the middle. This notochord and precordal plate will release growth factors telling the ectoderm cells to begin the formation of the neural plate. (The first organ system from the ectoderm is the CNS)
Day 18
Day 19
The mesoderm differentiates into the paraxial mesoderm, intermediate mesoderm, and lateral mesoderm. Paraxial mesoderm will become the somites. Intermediate mesoderm will become the kidneys and urogenital system. Convergence and extension and inductive intercellular signaling of the mesoderm cells allows the mesoderm to form the three regions. The signaling also allows it to communicate with endoderm and ectoderm.
d20-21 Blue arrows show the amniotic sac and trilaminar disc are growing faster around the secondary yolk sac. Tube in a tube growth. After the Somatic mesoderm grows over the splanchnopleuric mesoderm it forms the intraembryonic cavity/coelom which is a fluid filled cavity.
Day 20
Day 21
Day 25
Day 27
Embryonic folding has begun with the Embryonic disk and amniotic disk growing faster than the yolk sac endoderm. This is due to the convergence and extension of the mesoderm. Folding is a cause and an effect of organ development and placement (ex. Heart). True gut endoderm is at the "plate" and everything around the yolk sac is hypoblast cells.
The lateral plate mesoderm becomes the somatopleuric and splanchnopleuric mesoderm. The somateopleuric/somatic mesoderm becomes the lining of the body wall. The splanchnopleuric/splanchnic mesoderm will become the circulatory system. d21
day 24-25 regions of the head fold and heart is encased by the three layers. Yolk sac and the extraembryonic mesoderm will form the umbilical cord.
Splanchnic and intermediate mesoderm pushes together to contact to surround the gut tube forming the dorsal mesentery to hold the gut tube in place and many endodermal organs. Note: he said the splanchnic mesoderm is what makes the mesentery The dorsal mesentery extends from the stomach to the cloacal region of the hindgut The intraembryonic coelom/cavity becomes the peritoneal cavity. The peritoneal cavity is lined by somatic mesoderm and the cavity will house most of the internal organs of the torso.
Endoderm is starting to differentiate into the foregut, hindgut, and midgut. Foregut is supplied with blood by the celiac artery, the midgut by the superior mesenteric and the hindgut by the inferior mesenteric.
Further development to include the allantois (will connect with umbilical cord) and the vitelline duct.
Stomach is forming in the foregut region. The posterior region of the stomach is expanding. The dorsal area of the stomach grows faster than the ventral. This will result in the greater curvature and lesser curvature. The left and right vagal branches are around this area.
Day 30
The stomach routes clockwise around the long axis. The stomach is held in place on the posterior side by the dorsal mesentery called the Dorsal mesomegastrium/mesentery. The Ventral mesogastrium/mesentery holds the stomach to the anterior body wall (liver will form here).
Day 28
Day 35
wk4-5 Liver bud (hepatic diverticulum) from the lesser/ventral mesentery is developing into the septum transversum (mesoderm that separates pericardial and peritoneal cavity and will become the diaphragm). Note: Liver comes from endoderm but grows within the mesenteries
Liver is developing and it is connected to the anterior abdominal wall via the falciform ligament and the lesser omentum holds it to the stomach.
d40 Liver rotates clockwise while it is still growing and leads to development of the greater omentum (sac) from the dorsal mesogastrium. The greater omentum is dangling from the stomach.
Day 40
Rotation of the liver is done. There is the formation of the lesser sac(omentum) that came from the lesser mesentery.
Day 42
W7 day 42 Midgut is forming derivatives of the small intestine. The primary intestinal loop temporarily herniates into the umbilicus (temporarily leaves the body).
Week 7
Primary intestinal loops rotates 90 degrees.
Primary intestinal loop rotates another 180 degrees for a total of 270.
Primary intestinal loop completes rotations and comes back into the cavity. The cecum rests just inferior to the liver.
Week 8
Week 9
Week 10
wk 12Cecum descends pulling down the proximal hindgut forming the ascending colon.
Week 11
Week 12
Week 13
wk 14 The small intestine undergoes numerous rotations, elongates, herniates, retractions, and displacements to form the final Gastrointestinal tract. The GI tract is formed and the organs mature and grow. The imagine is a view from the anterior side of the gut. The mesoderm gives rise to the space these organs grow into and form the greater and lesser omentums.
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Week 14
Endoderm
Cloacal Membrane will divide/bifurcate via urorectal septum growing towards the membrane.
Cloacal Membrane divides into the Anorectal canal (anus) and Urogential sinus (system). Allantois, a vestigial organ (temporary organ) works only for 5 days to remove waste material and then it attaches to the placenta.
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Foregut gives rise to the duodenal foregut and then to the dorsal and ventral pancreatic buds which is inferior to the stomach. Ventral pancreatic bud grows into the ventral mesentery and the dorsal pancreatic bud grows into the dorsal mesentery. Buds are solid epithelial clusters that feel like hard nodules. Also there is formation of the cystic diverticulum.
Ventral pancreatic bud rotates clockwise to fuse with the dorsal pancreatic bud. The ventral pancreatic's duct will become the main pancreatic duct.
Pancreatic Cell Information
Respiratory diverticulum protrudes from the foregut. This sets up a proximal/distal axis of proximal and distal respiratory epithelium. The picture on the right is the view from inside the esophagotracheal ridge.
Respiratory Diverticulum buds into the left and right lung divisions. Beginning of the pseudo-glandular period - where the purpose is to expand the terminal bronchi (ends lobes) via budding and bifurcation into the visceral pleura and establish to parietal pleura (separates the body cavity from the lungs and comes from the somatic mesoderm)
Buds are proliferating into mesenchyme (type of cell that happens to be mesoderm at this point) growing caudally and laterally into the pericardioperitoneal canals. Mesoderm covering the buds and bronchioles becomes the Visceral Pleura. Secondary buds are the future 3 lobes of the right lung and 2 of the left. Secondary buds become known as secondary bronchioles when they are well formed.
The primordial pharynx is developing. The ridges grow and the ridges 4 and 5 fuse. This will lead to separating the lungs from the esophagus. Note: The tissue inside the arches is mesodermal (splanchnic mesoderm*) and neural crest cells will become cartilage and the musculature) but the tissue lining the arches is endoderm.
Arytenoid swelling arise from mesoderm proliferation between arches 4 and 6 around the laryngotracheal orifice. The laryngeal orifice is a T-shape bordered by the epiglottal swelling (hypobranchial eminence) which is formed due to proliferation of Arch 3 and 4 and the caudal part of it lines laryngeal orifice (primordial glottis).
wk7.5 Underlying mesoderm and neural crest are proliferating and signal the caudal portion of the epiglottal swelling (hypobranchial eminence) of the larynx to proliferate. This closes the laryngeal orifice(primortial
glottis).
wk10The laryngeal orifice (primordial glottis) is recanalized and the epiglottal swelling becomes the epiglottis. This allows the lungs to be bathed by amniotic fluid.
The Superior Laryngeal Branch of the 10th Cranial Nerve (CNX) innervates derivates of the 4th arch.
The Recurrent laryngeal Branch of the CNX innervates derivatives of the 6th arch,
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Formation of tertiary bronchioles. There are 10 in the right lung and 8 in the left. The bronchial smooth muscles, capillaries, and connective tissue arise from the splanchnic mesoderm.
Canalicular stage begins. Tertiary bronchi differentiate into respiratory bronchi within the visceral pleura. They begin to associate and come close to capillaries nearby. Continue to grow into the mesoderm.
17 generations of budding has occurred which shows the final shape of the lungs. That means 2^17 divisions
Week 15
Week 16
Week 17
Week 18
Week 19
Week 20
Week 21
Week 22
Week 23
Week 24
Week 25
Some tertiary bronchi differentiate into terminal alveolar sacs (site of gas exchange in the lung). May be able to support life outside the womb. The Terminal Sac Stage begins and start of he third trimester. Purpose in this stage is for endothelial cells (simple cuboidal) liming the terminal alveolar sacs to begin expressing cell adhesion proteins t help the cells flatten. They become type 1 alveolar epithelial (simple squamous) Flattening allows cells allows the terminal alveolar sacs and the capillaries to come in close contact to facilitate gas exchange and having a larger surface area to do so.
Week 26
Week 27
Week 28
Week 29
Week 30
Week 31
Week 32
Week 33
Week 34
Week 35
Week 36
Week 37
Week 38
Week 39
Week 40 / Birth
Type 2 Alveolar Epithelial cells arise as cuboidal and may become pseudostratified. They produce surfactant a phospholipid rich fluid which coats the entire surface of the terminal alveolar sacs to lower the surface tension. Necessary for breathing. Genes that make surfactant: TTF-1, HNF-3, Glucocorticoids, Thyroxine, and Surfactant A/B.
Alveolar Stage begins. Alveoli form up to 10 years old. Purpose is to provide prepare for a terrestrial environment for gas exchange as opposed to the placental/aqueous one. 3 things must occur: Surfactant production, proper differentiate of cells for gas exchange, establish pulmonary and systemic circulations.
10 Years Old
As the lung mature the alveoli do not get bigger, you simply get more. Between birth and now an additional 6 - 7 divisions occur. Alveoli finish forming.
Note: Lungs and larynx are forming at the same time,
Folding of the embryo begins between days 15 - 18
Molecular Control of Lung Development
BMP4 is secreted by the distal endoderm onto the endoderm and mesoderm.
BMP4 secretion leads to stimulating of the mesoderm to release Noggin. Example of paracrine signaling
FGF10 - Maintain distal respiratory epithelia. May promote branching.
Sonic Hedgehog (SHH). Vital in lung development
Binding onto it self (autocrine signaling) it activates the following receptors:
Type1 ALK2, ALK3, ALK6 and Type 2 BMPRII, ACTRII
These two drive lung shape.
Leads to BMP4 driving the bud formation. And beginning to secrete noggin, but not enough to inhibit the BMP4 action on the endoderm
Noggin is able to bind up enough BMP4 to prevent growth and bud formation. But only in that one area with the white X. Leads to bud bifurcation. Happens 2^23 times.
We know BMP4 begins the bud due to LacZ reporter gene staining.
When you stain lung buds you only see it at the terminal ends of them.
Noggin is secreted by the mesoderm surrounding the distal endoderm.
It is a natural inhibitor of BMP4 by binding it (like a sponge). It does not affect the transcription of translation of BMP4.
Molecular Control of Tongue Formation
BMP7 is the same thing as BMP4 but BMP7 causes little proliferation in the endoderm. Is expressed in gradient fashion.
Noggin is secreted by the mesoderm surrounding the distal endoderm.
It is a natural inhibitor of BMP7 by binding it (like a sponge). It does not affect the transcription of translation of BMP47. Note: Noggin inhibits all BMPs.
Patched (Ptc) a secrete protein. Secreted in gradient fashion. Drives proliferation of endoderm cells.
Noggin is secreted by the underlying mesoderm of the pharyngeal arches.
BMPs are natural inhibitors of Ptc which leads to a battle between Ptc and BMP
Over time Noggin inhibits BMP7.
BMP7 is inhibited therefore they are no long inhibiting Ptc. Ptc is free to act. The endoderm then proliferates with the mesoderm to form the tongue.
Similar processes occur for the pancreas, liver, and other organs.
check this somatic mesoderm from mints
check this splanchnic mesoderm from mints
check this somatic mesoderm from mints
Mesoderm
Extraembryonic cavity/coelum is the source of all cavities including:
- Pericardial cavity surrounds the heart
- Parietal pleura that encapsulates the pleural cavity around the lungs (it covers the thoracic cage the lungs are in)
- Pleural cavity
Other Cavities forming due to growth and folding of the mesoderm.
Intraperitoneal cavity is what is housing the gut tube.
Retroperitoneal cavity (dorsal) houses the aorta.
Retroperitoneal cavity (ventral) houses the bladder.
Paraxial Mesoderm aka Somitic Mesoderm
Somites Begin to Develop. You will get 40 pairs of somites. The start developing at the mid region of the back and then cranially and caudally. Each has functional parts.
- Sclerotome cells make vertebrae, bones, and cartilage.
- Dermatome cells forms dermis of skin on dorsum of body
- Myotome cells form skeletal muscle of the neck, trunk, and limbs
Intermediate Mesoderm.
wk7-8 Thoracic, head, and neck muscle begin to develop. Myotome divides into a dorsal epimere and ventral/lateral hypomere.
- Epimere - Erector spinae muscle
- Hypomere - transversospinalis, hypaxials, rectus abdominous
The limb buds themselves come from the somatopleuric lateral plate mesoderm but premyogenic cells (progenitor cells fro myotomes) migrate from the myotome into the limb buds. These progenitors form a ventral and dorsal muscle mass. #
Bone Ossification Note: This series does not follow a timeline.
Endochondral ossification - cartilage model forms first then ossifies. Forms axial skeleton bones such as vertebrae, ribs, sternum, cranial base, and limbs.
Cell Types
Chondrocytes - secrete cartilage
Osteoblasts - secrete bone matrix
Osteoclasts - resorb bone. Work with osteoblasts to regulate intramembranous ossification
Long Bone Formation - occurs in layers or compartments due to Sclertomes, a type of somite progenitor cell.
Epiphysis - Compartment of cartilage growth from progenitor cells. Consist of layers of resting chondrocytes.
Diaphysis - compartment of proliferating chondrocytes. 3 Layers:
- Proliferating chondrocytes
- Prehypertrophic condrocytes - chondrocytes that have enlarged
- Hypertrophic Chondrocytes - Cells that are surrounded by calcified matrix and they secrete collagen. Eventually replaced by osteoblasts.
Vasculaturization of hypertrophic region needed for invasion by osteoblasts. These osteoblasts secrete Type 1 Collagen and mineral matrices which from a primary spongiosa. Primary spongiosa becomes the Primary Ossifcation Center (POC)
POC grows as the 2 epiphyses move in either direction by proliferating chondrocytes. A bone collar forms around the diaphysis.
At birth, there are growth plates (epiphyseal cartilage plates) between the epiphysis and proliferating chondrocytes of the diaphysis. Ossification of the growth plate happens in late teens.
Intramembranous ossification - bone forms from mesenchyme or neural crest cells. Forms bones of the face and cranial vault.
Process:
- Mesenchyme condenses into sheets
- Osteoblasts from vasculature are entrapped into the sheet and secrete collagen
- Mineralization from osteoblasts for trabeculae forming a spongy bone
- Spongy bone is filled in by continuous mineralization.
wk6 Joints between developing bone begin to form. Three Classifications.
Cartilaginous - Mesenchyme differentiate into a fibrous/cartilaginous tissue.
Ex. Pubic symphysis, costo-chondral joints
Synovial
- Mesenchyme peripheral to two bones condense into capsular and ligament tissue
- Central mesenchyme undergoes apoptosis leaving a fluid-filled synovial region
- Synovial membrane forms on the bone surfaces
Ex. Knee Joint
Fibrous - Mesenchyme between bones differentiate into dense fibrous tissue.
Ex. Sutures between cranial plates
wk8 Joints resemble adult joints.
Other Somite Cells
Syndotome forms tendon
Endothelial Cells form the lining of the blood vessels
At week 3-4 the intermediate mesoderm begins to from the earliest progenitors of the urogenital tract.
Somatic Mesoderm has begun to grow over the splanchnopleuric mesoderm to form the intraembryonic cavity. wk3-4
Wk2 Primary Heart Field forms from the first cells that passed through the primitive streak to become mesoderm cells. A secondary heart field will form and that will give it 3D shape. The heart is the first organ to form. #
Cardiogenic area of the lateral plate mesoderm is apparent. The cardiogenic part is on the cranial/cephalic end of embryo. It is communicating via morphogens and direct contact with the endoderm to begin the formation of the heart. By day 14-15 there could be rhythmic beating..
The primary heart field looks like this at day 15.
Splanchnic Mesoderm makes the visceral pleura over the lungs
d21 The lateral plate mesoderm folds and it brings the two lobes together so they can fuse. This structure is called a heart tube. Blood is being pumped through this tube. When folding occurs it is now a secondary heart field. The left and right atria are also visible.It is also supplying the embryo with blood.
d 22Bulbos Cordis (conotruncal valve) forms a major portion of the pulmonary artery. The inferior portion will beat and the inferior portion will not. The sinus venosus region gives rise to the superior and inferior vena cava which are both responsible for blood return to the heart.
Day 23
d 24
d28 Atrium loop up. The aortic arches form from the Aortic Sac (AS). Looping due to communication between mesoderm and endodermal cells
d50 the heart and its major vessels are in place pumping blood.
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Note: this branch is not based on a timeline except where labeled.
Growth of the Heart
As embryo gets larger it needs more blood cells to supply oxygen resulting in an increased hemodynamic load. The more pressure from this load the more the heart needs to grow inducing cardiomyocyte proliferation.
Valves are important for control flow of blood. The form first as a regional swelling of the extracellular matrix secreted from cardiomyocytes. The swellings are called cardiac cushions. AVV fused with the LV at Day 28 and the AV cushion becomes the AVV at Day 50. Cushion is a name for a "pre-valve".
Blood islands start to develop in the definitive/secondary yolk sac in the extraembryonic mesoderm where there is low oxygen. Extracellular matrix is around the endoderm of the secondary yolk sac. Vasculogenesis is the formation of the arteries and veins. Angiogenesis is the branching of the existing ones.
Mesenchyme cells begin to cluster (angiogenetic cell cluster) and differentiate into hemangioblasts. This is due to oxygen sensitive genes in the mesenchyme cell (HIF1-alpha). Low oxygen leads to increased HIF1-alpha expression which leads to VEGF mRNA production. It has autocrine and paracrine action.
Further differentiation of the hemangioblasts produce both primitive blood cells from the cells inside the cluster (RBC are nucleated at this stage) and endothelial cells lining capillaries from cells on the periphery of the cluster.
Blood formation begins in the secondary yolk sac. d17
1st hepatic colonization occurs where mesoderm cells migrate to the liver. There are definitive hematopoietic stem cells (dHSCs) populating the liver. d23
Mesenchymal cells of the extraembryonic mesoderm express Flt1 (VEGF-R1) and Flk1 (VEGF-R2) that bind VEGF. When activated by VEGF they differentiate into the clusters.
- Flt1 will be released as sFlt1 that gets released into the blood
- PLGF (Placental Growth Factor) is a type of VEGF
dbl check the second bullet here
Arterial clusters (angiogenic cell clusters/blood islands) begin to fuse to make capillaries, vessels and blood. d27
Second hepatic colonization as more mesodermal cells colonize to create more blood vessels in the liver. d30
Bone marrow colonization. dHSCs migrate to the long bone marrow and become definitive hematopoietic stem cells. these cells give rise to multipotential (progentior) stem cells. They can become myeloid or lymphoid progenitor cells. wk10 Bone marrow development sites. Bone marrow is made in the bones at the places shaded in blue.
Neuregulin is a gene involved in the growth of the heart and proliferation of the cardiomyocytes. It acts as a paracrine factor.
Oxygenated blood enters the fetus via the umbilical vein and the ductus venosus will shunt this blood from the developing liver towards the heart.
The oxygenated blood from the ductus venosus shunt passes through the inferior vena cava into the right atrium. The foramen ovale (hole between the two atria) will allow blood to move from the right atrium to the left atrium. The ductus arteriosus connects the aorta (to the body) to the pulmonary artery (to the lungs) this allows blood to shunt towards the aorta as your lungs do not oxygenate your blood yet. The blood travels through the whole body, and then exits the to the placenta via the umbilical artery.
Circulatory System
Arterial System
Aortic Arch Region
Venous System
Dorsal Aortic Region
Umbilical vessels subregion goes to the placenta
The indent between the arches are called pharyngeal pouches. Inside the mesoderm of the arch the aortic arches exist which all connect to the aortic region (future aorta) near the anterior part of the bulbus cordis. Each arch has its own population of neural crest and mesoderm cells. Remember mesoderm becomes the blood vessels due to VEGF acting.
- Arch 1 supplies the maxially bones
- Arch 2 supplies the mandible of the jaw
- Arch 3 and 4 supply the neck
- Arch 6 Supplies organs of the thorax
The Vitelline vessels connect the embryo circulation to the yolk sac, and the dorsal branches are for supplying the vertebral column, body wall, and limbs.
Lateral Branches will supply the kidneys and gonads
Dorsal Intersegmental branches will supply the vertebral column, body wall, and limbs.
Ventral Vitellin Vessel Subregion - Will supply blood to the GI tract. Lots of them looks web like and eventually will fuse.
Umbilical region
Vitelline Region
Cardinal Region is from early development the majority of it will disappear - it is the original venous system.
Truncus arteriosus forms on the anterior portion of the heart tube. A lot of the aortic arch arteries come from this. d21
Truncus arteriosus becomes the aortic sac then it divides into aortic arch arteries. (Due to Hox genes) d24
Arch of the Aorta comes from the 4th pharyngeal arch. The pulmonary artery comes from the 6th pharyngeal arch. The dorsal aorta becomes the external carotid artery and the ventral aorta becomes the internal carotid artery.
Axial Arteries arise due to vasculogenesis from the somatopleuric lateral plate mesoderm. d27 #
By 7 weeks the vitelline arteries have restructured to give rise to the arteries for the gut.
- Celiac Artery - foregut
- Superior mesenteric artery - midgut
- Inferior mesenteric artery - hindgut
Intersegmental artery grow from the dorsal aorta to come in close contact with the axial artery. d30 Axial artery is extending with the muscle progenitors and ventral and dorsal masses.
Intersegmental arteries emanate from the dorsal aorta and will come close to the axial artery. #
Lower axial arteries arise via vasculogenesis from the somatopleuric lateral plate mesoderm. They grow quickly to become the external iliac artery. It is the initial site for nearly all the arteries of the leg. d35
Two arteries that develop directly from the axial artery.
- Brachial Artery of the upper arm
-- Axial artery basically became this artery - Interosseous Artery of the lower arm
Early Bloodflow Chart!
Later Blood Flow 8 monthes
Blood Flow at Birth. Several changes are necessary.
- Ductus Arteriosus must constrict - forms the ligamentum arteriosum - within 24hrs
- Umbilical veins constrict and degrade
- Oval Foramen must close - initially controlled via increased pressure in the left atrium - then physically seals shut (3-7days)
Endothelial cells from major veins undergo bilateral angiogenesis It under goes vasculogenesis - just not blood vessels. week6
The jugular right and left lymphatic sacs develop. They will drain lymph from the upper limbs, trunk, head and neck.d56
After the sacs grow the retroperitoneal sac, cisterna chyli, and posterior sac develop. Cisterna chyli drain lymph into the thoracic duct which then empties it into the venous circulation. week 16
Limb buds form from the somatopleuric lateral plate mesoderm.
Ventral and Dorsal Muscle Masses move as mesodermal progenitor cells. Once they get there they become mono nucleated myoblasts and then fuse with other cells to become multi-nucleated myotube. The then become innervated to become innervated mature myofibre and come together with others to be a functional motor unit.
Sclerotome
Costal Processes form from the sclerotomes within the thoracic region and elongate along the body wall surrounding the heart. wk5
The first seven ribs connect ventrally and cranially to the mesenchymal condensates (sternal bars) which ossify to make the sternum. Fusion happens in the caudal direction
During Fetal period and by birth the mid-regions of the sternum have ossified while the regions connect to the bone are cartilage still. The xiphoid process will not ossify until birth.
Ectoderm
Once the primitive streak regresses the cells left in the epiblast layer are the true ectoderm.
The notochord releases SHH to direct the ectoderm to involute into the mesodermal space. SHH is responsible for ventralizing the neural tube. It forms the neural groove and neural fold.
Neural folds continue their convergent/extension approach and Neural Groove is developing. Some cells from the edge of the neural fold fall off into the mesoderm area to become neural crest cells. Neural crests cells will become facial bones and spinal ganglia of the PNS. Fusion between the edges is over time starting from the middle extending to the ends.
Cranial portion (anterior neuropore) of the neural tube finally closes. d25
Caudal end of the neural tube (posterior neuropore) fuses. d27
Can morphologically differentiate between the anterior head region and the tail region. d 24-25
Yolk sac fluid contains over 300 microRNAs. These are small 21 ribonucleotide long molecules that bind to the 3' untranslated region of a gene mRNA transcript decrease or help control the amount of mRNA is translated. Can silence genes on the notochord process which allows other genes to turn on.
BMP and Wnts come from the surrounding epithelial-like tissue of the ectoderm. Noggin comes from the mesoderm. Wnts are responsible for the majority of dorsalizing of the neural tube. Too much Wnts = possible bifurcated head. BMP and Wnts can affect the mesoderm but noggin helps prevent that.
Neuroectoderm (neuroepithelium) is what the neural tube is called at this point. Made of undefined pseudo-stratified columnar epithelium has adhesion junctions. Has a little external membrane. Neural Crest Cells ectoderm in nature. Lots of mesenchymal mesoderm walking around.
Noggin acts to stop BMP activity so that the dorsal region of the neural tube can differentiate into the glia and neurons. Undefined neuroectoderm begins to differentiate into distinct layers.
- Ventricular Zone - inner layer of cells that give rise to all neurons and glia.
Parts of the early spinal cord. d40 #
Alar plate - dorsal region of the developing spinal cord. Will become afferent interneurons.
Basal Plate - Ventral region of the developing spinal cord. Will become efferent neurons. Cell bodies stay in the spinal cord.
Sulcus limitans - Seperates alar and basal plates. Will become the lateral horn.
Roof and Floor plate - Regions where neurons can transverse the top and bottom of the neural tube, respectively.
Neural Crest Cells also form the dorsal root ganglia - axons extend into the dorsal region of the spinal cord.
These cells also form sympathetic neurons, Schwann cells, melanocytes, odontoblasts, meninges, and bones of the face and pharyngeal arches.
Intermediate zone cells will begin to differentiate.
- Intermediate Zone - Contains cells from ventricular zone that have begun to differentiate into neurons or glioblasts.
- Marginal Zone - Will form the white matter of the spinal cord.
- Spinal Meninges - Come from mesenchyme around the paraxial mesoderm. Mesenchyme condenses to form a membrane, primordial meninx which will become meninges
- External Cells become the Dura mater and the Internal Cells become the Pia mater and arachnoid mater which come from neural crest cells. Shows a mixing of mesoderm (mesenchyme) and ectoderm(neural crest) cells.
All layers visible by day 60
BMP and Wnts are affected the roof plate and the SHH (from notochord) affects the floor plate. Work together to shape the vertebra. As the plates move closer the central canal gets smaller. d40-60
Can tell the difference between grey and white matter. d60
Dorsal root ganglion - shows the cell bodies of the sensory neurons just outside the dorsal root. Alar plate axons synpase in the brain. Basal plate motor neurons extend to the peripheral nervous system. wk9
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Notochord will eventually undergo apoptosis or else they pump out SHH and causes diseases.
From the neural plate region the cranial portion of the neural tube becomes the: Prosencephalon (forebrain), Mesencephalon (midbrain), and the Rhombencephalon (hindbrian). wk4
The "top" part of the neural tube undergoes convergence and extension. and new regions such as the optic vesicle, pons, medulla, and hemispheres have begun to appear. This is also controlled by the folding of the lateral plate mesoderm and amniotic sac. wk5
Gyri folds in cerebral cortex beging forming. Allows to distinguish human from mouse brains. These are primary cortical gyri. Gyrification give a larger cortical surface area gives rise to greater cognitive functionally - fitter a larger brain into a smaller cranium.
Secondary gyri folds appear. w10
Cerebral hemispheres within the telencephalon grow rapidly. w13
Tertiary gyri folds appear. The cerebral hemisphere takes on a horseshoe shape. The hemispheres will grow in a circle from caudal to cranial. From now to birth the cortex will grow to cover the diencephalon, part of the cerebellum and most of the pons. w24-26
Three folding theories.
Axonal Tension - Axons act as wires that pull cortical areas close to each other to cause gyrification.
Differential tangential expansion - Different amounts and rate of neurons and support cells dividing between different areas. Gyri (bumps) are made in areas of high production and sulcus (indent) is made in low areas.
Mechanical Buckling - Forced induced changes. Like trying to fit a blanket by stuffing it into a container. Stochastic way of gyrification and would cause random distribution of gyri. Incorrect because they are not random.
Progenitor cells in the ventricular zone (radial glial cells) begin to do asymmetric cell division - parents cells will be smaller than daughter cells. Daughter cells are true progenitors that will become neurons and glial cells depending on location and what signals they are receiving. Neurons come first and glial cells later. wk5
Glial cells start to arise in the form of astrocytes, oligodendrocytes, and microglia.
Pyramidal neurons travel along projections or spoke of other radial glial cells to reach near the marginal zone of the cerebral cortex which near the grey matter. These neurons goto the sub ventricular zone (between the ventricular and intermediate zones and wait for 1 day. The radial glial cell will direct the pyramidal cell to where it should go. 6 levels of pyramidal neurons develop in the grey matter.
Please Note: The information and pictures included in this "timeline" either came from Dr. Gallicano's (Georgetown University) lectures, primers, class notes, MINTS, and some "clarifying" information came from an reputable internet resource. Do not copy, or otherwise redistribute.
Update Log
(any edits will be posted here)
9/22/17 - Moved over Ectoderm Primer info - accidently put it on the wrong image last week. SORRY!
Made clear
"Epiblast cells that are to become mesodermal cells enter the space as mesenchymal cells, which is their cell TYPE, as opposed to be a cubodial or columnar type cell."
9/20/17 - Fixed Laryngeal/pharynx slide at day 40 (incomplete sentence)
Ectoderm overlying the mesoderm is one cell layer thick. wk4
Two layers are present. Surface ectoderm becomes the basal layer. Forms a new layer periderm. This layer will keratinize and desquamates (sheds). These cells can be used for stem cell research. Periderm secretes waxy substance, Vernix Caseosa, which protects the developing epidermis from urine and other substances in the amniotic fluid and helps with the birthing process. wk7
Basal layer continues to divide giving multiple layers. This includes the intermediate layer of undefined keratinizing epidermal cells. wk11
Epidermis is virtually completely developed and all hair follicles are in place that will be at the time of birth. Basal Layer (stratum germinativum) gives rise to defined lineages and layers. There are four layers above it: Stratum Spinosum, Stratum Granulosum, Stratum Lucidum, and Stratum Corneum. The stratum corneum is the layer that is sloughed off. The melanocytes present are from the Mesoderm, they migrate into the basal layer of the epidermis. wk26
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