ANA301 Test #2

What are pleural cavities

Space between the parietal and visceral pleural linings. Parietal is adjacent to inner surface of ribs, visceral is adjacent to lung tissue.

Parietal --> pleural cavity --> Visceral

Function of trachea

Passage of air as we inspire and expire with c shaped hyaline cartilage rings that open to allow movement of esophageal contents. (T4/5)

Function of the bronchi

Continued passage of inspired and expired air

Discuss the different bronchi

Right primary bronchi: wider shorter and vertical

Left primary bronchi: narrow longer and horizontal

Secondary bronchi: within lung lobes 2 on the left and 3 on the right

Tertiary bronchi: within lung segments 10 on the left and right

Lung function and structure

It is where gas exchange occurs and is large with light weight tissue. Has a narrow apex and wide base and has two lobes on the left and three on the right which are separated by deep grooves called fissures.

Which lung is the cardiac notch on

left

What is the root and hilum

root: collection of tubular structures attached to deeper lung tissues

hilum: pleura surrounding the root

In each root and hilum is: pulmonary artery, two pulmonary veins, primary bronchus and bronchial vessels, nerves and lymphatics.

Laryngotracheal diverticulum

Something called the laryngotracheal groove in the floor of the pharynx

Ventral growth during 4th week results in the laryngotracheal diverticulum. Which elongates to form the globular respiratory bud.

As this occurs the diverticulum begins to separate from primordial pharynx via tracheoesophageal folds which eventually fuse to create the tracheoesophageal septum.

What is the point of connection between the primordial pharynx and developing trachea

laryngeal inlet, and this is the part where the pharynx and trachea are continuous with each other

tracheoesophageal fistula

Abnormal passage between trachea and esophagus which is caused by incomplete division of the cranial segment of the tracheoesophageal septum in the 4th week. Mostly males affected and 1/3000 to 1/45000 live births.

polyhydramnios occurs (excessive amniotic fluid) due to failure of fetus to swallow

Development of the bronchi

Initial respiratory bud at caudal end of laryngotracheal tube divides into two primary bronchial buds will continue to divide over and over so that we will eventually get a bronchial tree.

As the branching occurs splanchnic mesoderm will also proliferate and turn into cartilage around the structures of the lung.

Development of pleural cavity

Lateral edges pinch off the yolk sac and as they fully enclose the gut the intraembryonic body cavity surrounds the primitive gut which is suspended in the cavity by dorsal mesentery.

By the end of the fourth week the somatic (parietal) and splanchnic (visceral) mesoderm layers line the intraembryonic coelom.

Discuss the intraembryonic cavity and the pericardial, peritoneal cavitie(s) and pericardioperitoneal canals

Formed by lateral edges of the embryo into a horseshoe shape before head folding occurs.

Pericardial cavity at cranial end and contains the heart, peritoneal cavity at caudal end and contains the lungs , connected by the pericardioperitoneal canal.

Development of lung pleura

Tracheoesophageal tube has a canal on each side and the lungs will develop and push into the canals.

Canals lined with visceral and parietal pleura. As bronchial buds grow, they push into the canals and eventually contact parietal pleura. As lungs continue to grow visceral pleura pushes into the sides of the canal and the parietal pleura surrounds it giving you the pleural lining.

4 stages of lung maturation

Pseudoglandular, Canalicular, Terminal Sac, Alveolar

Pseudoglandular stage

5-17 weeks. Gas exchange cannot happen because the oxygen in the terminal bronchiole is too far from the capillary. Therefore fetus is not viable.

Canalicular stage

16-26 weeks. Some of the capillaries have gotten close to the conducting tube epithelium so they form a better bond and there is an increase in vascularization. Branching happens so there is larger luminal space and respiration is now possible around 24-26 weeks because terminal sacs (primordial alveoli) have developed at the ends of respiratory bronchioles.

Terminal Sac Stage

24 weeks to birth. Development of the terminal sacs occurs distal to conducting tube. Pulmonary capillaries and conducting tube epithelium are now very close together. Eventually the terminal sacs turn into alveoli and are lined by type 1 and type 2 pneumocytes (more type 1) type 1 are squamous epithelial cells of endodermal origin and type 2 are roundish secretory epithelial cells that secrete surfactant. Even though we have less type 2, they are vital because we need surfactant in order for respiration to occur.

Alveolar Stage

Fetal period to 8 years. 7 more divisions and and maturation at the level of the terminal sacs into alveoli. There is an increase in type 2 pneumocytes to enhance surfactant secretion.

Surfactant

Phospholipid and protein secreted from type 2 pneumocytes. The production begins around 20-22 weeks but is not sufficient until the terminal stages of pregnancy. Around 26-28 weeks the survival is possible. Its purpose is to reduce alveolar surface tension and increase lung compliance

respiratory distress

Lots of respiratory energy needed to open the collapsed alveolar spaces due to a lack in surfactant.

Diaphragm

Forms the physical division between the thoracic and abdominal cavities and consists of the central tendon (heart above) and striated muscle fibers which we can control (when taking deep breath) they extend inferiorly via columns called crura. At the centre close to the central tendon are 3 openings created which are tube structures running from thorax to abdomen

3 openings in diaphragm

Vena Cava (thoracic vertebrae 8)

Oesophageal (thoracic vertebrae 10)

Aortic (thoracic vertebrae 12)

Four stages of diaphragm development

Septum transversum, Pleuroperitoneal membranes, Dorsal mesentery of esophagus, Muscular ingrowth from body wall.

septum transversum

During 3rd week of development the septum transversum is cranial to heart but it ends up forming the heart so we need to flip it caudally via head folding ventrally during the 4th week. It then grows dorsally from the ventrolateral body wall to form a shelf separating heart from liver and than expands and fuses with the mesenchyme ventral to the esophagus and pleuroperitoneal membranes.

pleuroperitoneal membranes

Fuses with the septum transversum and dorsal mesentery of the esophagus to seal off the pericardioperitoneal canals in the 6th week ventrally and medially (right one first and ) to form the primordial diaphragm. This is a large portion of fetal diaphragm but small portion of infants diaphragm.

Dorsal mesentary of esophagus

The vena cava and aorta Hiati will be created from the dorsal mesentery of the esophagus and will make up the central portion of the adult diaphragm. Septum transversum and pleuroperitoneal folds will fuse with the dorsal mesentery. Eventually myoblasts grow into the dorsal mesentery and grow downwards to form the crura on either side.

Muscular ingrowth from body wall

Insignificant in early embryo but substantive in the neonate and adult. The muscular ingrowth will turn into the striated muscle and make up the majority of the diaphragm.

Diaphragmatic hernia

Posterolateral defect of diaphragm effects 1/3000 live births and can cause a congenital diaphragmatic hernia which is the herniation of abdominal contents into the thoracic cavity. Usually this happens because the pleuroperitoneal membrane does not properly fuse with the other parts of the diaphragm (ST or DME) and if a canal is still open when the intestines return to the abdomen from umbilical cord some may pass through the defect into the thorax. This all can cause pulmonary hypoplasia.

Pharynx

Throat with three regions, two being part of digestive system: oropharynx - continuous with oral cavity

laryngopharynx - continuous with larynx (into trachea and ending at esophagus)

Esophagus

Begins distally (at the base of) laryngopharynx and passes through the thorax piercing the diaphragm at T10 and connecting to the stomach.

In the thorax it is posterior to the trachea and medial to the thoracic aorta.

When it passes through the diaphragm it is passing through the esophageal hiatus so we call it the abdominal esophagus which is the initial segment of the foregut and connects to stomach

Stomach anatomy

Connects upwards to abdominal esophagus and this region is called the cardia because it is so close to the heart.

Fundus of stomach - blind end

Body of stomach - largest component

Pylorus region - where food contents exit stomach, pyloric sphincter and connects to small intestine.

Development of stomach involves rotation, so we use greater and lesser curvature as reference.

We can see fat connecting the lesser curvature of stomach to the liver , this is called the lesser omentum.

Large layer of fat connects greater curvature of stomach this is called greater momentum and covers the intestines. Anterior to intestines.

small intestine

Chyme leaves stomach and enters small intestine through pyloric sphincter and the small intestine has three subdivisions from proximal to distal.

Duodenum: most proximal, it is C shaped and has four parts.

- superior

- descending (where duodenal papilla is and where enzymes push into duodenum)

- inferior (horizontal)

- ascending

Jejunem

Ileum.

small intestine does not refer to the space but rather how big the lumen is

ileocecal junction

Connection of the small intestine (ileum) to the large intestine (cecum). The cecum is the looping part of the large intestine. The appendix is attached to the cecum.

Large Intestine

Cecum extends downwards

Ascending colon goes back upwards.

Two flexures.

- Where transverse colon goes across this is called the right colic flexure (hepatic) and the liver is very close here

- Flexure with descending colon is called the left colic flexure (splenic flexure) and the spleen is very close here.

Sigmoid colon

Rectum

Anal canal

Anus

It is wider but shorter than small intestine.

2/3 across the transverse colon is the delineation between midgut and hindgut

Pancreas

Located between duodenum and spleen. Alkaline Pancreatic enzymes travel along pancreatic duct to enter the small intestine at the major duodenal papilla and just inferior to the major duodenal papilla is the delineation between foregut and midgut. On the inside of the duodenum is an opening which connects bile duct to the pancreatic duct. This will carry bile from the liver and pancreatic enzymes from the pancreas into the duodenum.

Consists of: uncinate process, head, neck, body, tail.

Pancreas is located behind the stomach.

Liver

Liver is located under the right dome of the diaphragm and has 4 anatomical divisions:

- Right lobe

- Left lobe which is separated from right lobe by the falciform ligament

- Caudate lobe which is on the inferior, posterior surface of the liver and adjacent to the inferior vena cava

- Quadrate lobe which is on the inferior , anterior surface of the liver and is adjacent to the gall bladder

Bile from the liver travels along the hepatic duct system to enter the duodenum at the major duodenal papilla.

Gallbladder

Located adjacent to the liver. Stores and concentrates bile for future use. its ducts join the hepatic duct system of the liver to secrete bile into the small intestine via the major duodenal papilla

Arterial supply of the GI system

Heart will pump oxygenated blood into the arch of the aorta, down the aorta and the aorta will pump out of the diaphragm at the aortic hiatus which will bifurcate into R and L vessels which go to limbs.

blood supply to each gut division and what determines transitions of gut divisions

Celiac trunk - foregut (liver, gallbladder, pancreas, stomach, spleen)

Begins at abdominal esophagus, ends inferior to the major duodenal papilla

Superior mesenteric - midgut (majority of Small intestine and little bit of the large intestine)

Begins inferior to the major duodenal papilla, ends 2/3rds of the way along the transverse colon

inferior mesenteric - hindgut (remaining portion of large intestine and distal elements of anal canal)

Begins 2/3rds along the transverse colon and ends midway through anal canal

Oropharyngeal membrane

membrane which will cover the oral opening and eventually membrane breaks down and oral cavity will open to the surroundings

Where does the primordial liver develop

close to the arterial trunk of the foregut and pushes its way into the septum transversum

yolk stalk

omphaloenteric duct which extends out of the ventral aspect of the embryo

pharyngeal arch arteries

arteries connecting the dorsal aorta to the cranial parts of the heart and are found within the pharyngeal arches of the pharynx

Formation and Position of the Primitive Gut

Endoderm = epithelium and glands

Splanchnic mesoderm = muscles and connective tissue

Transverse folding is how the initial gut is formed. The entire gut tube will end up being surrounded by an intraembryonic body cavity. The dorsal mesentery suspends the developing gut into the intraembryonic body cavity and connects the embryonic duct to the dorsal abdominal wall. By the time transverse folding is complete the gut is suspended into abdominal cavity by a dorsal mesentery that extends entire gut tube.

Development of the Mesenteries

Abdominal viscera are either suspended...

within the peritoneal cavity by mesenteries (intraperitoneal)

or

adjacent to the posterior abdominal wall with overlying peritoneum (no mesentery) (retroperitoneal)

Peritoneum (retroperitoneal/intraperitoneal)

Peritoneum is a bubble within the abdominal cavity and sometimes structures end up pushing their way into the middle while others remain at the back.

Organs found outside of the bubble entirely like kidneys are retroperitoneal

Organs surrounded by a layer of bubble and extend into the cavity like ileum or jejunum are intraperitoneal

Mesentery

Double layer of visceral peritoneum that connects an intraperitoneal organ to the posterior abdominal wall.

Mesentery of jejunum and ileum = the mesentery (mesentery proper)

Mesentery of transverse colon = transverse mesocolon

Mesentery of the sigmoid colon = sigmoid mesocolon

Mesentery of appendix = mesoappendix

only part of the gut tract not suspended by mesentery

duodenum

Greater Omentum

double layer of peritoneum

greater and lesser momentums are reflections of peritoneum

connected to the greater curvature of stomach and extends down over the small intestine

Lesser omentum

lesser omentum connects stomach to the liver it is lesser in terms of its size and also its function.

omentums functionally are filled with lots of adipose tissue and lots of macrophages (they have some immune function)

Dorsal and ventral mesentery

Dorsal: attaches the primitive gut to the dorsal/posterior body wall of the embryo, from foregut to hindgut

Ventral: attaches only the foregut to the ventral/anterior body wall

Derivatives of the mesogastrium

Components of greater omentum

derivative of dorsal mesentery

greater omentum

derivatives of the ventral mesentery

falciform ligament which connects the anterior liver to the anterior abdominal wall. We see this ligament in the adult doing the same thing and within the falciform ligament is the round ligament , the adult derivative of the umbilical vein.

also lesser omentum

derivatives and blood supply of the foregut

Derivatives:

- primordial pharynx + its derivatives

- lower respiratory system

- esophagus

- stomach

- proximal small intestine: duodenum, up to major duodenal papilla

- liver

- biliary apparatus (hepatic ducts, gallbladder, bile duct)

- pancreas

all supplied by celiac trunk

Major duodenal papilla

allows for liver, pancreas and gallbladder to drain into the duodenum

Development of the Esophagus

Develops from the foregut immediately caudal to the pharynx. As it develops through its entire length it goes through occlusion and recanalization: the endoderm which lines the tube, proliferates so much that it fully occludes the tube of the esophagus forming an endoderm plug. The tube opens up with the recanalization step - where we see these vacuoles forming in the middle of the tube. The vacuoles join together forming that normal lumen.

Failed recanalization

if it fails it can be complete or incomplete

incomplete (partial) failure leads to esophageal stenosis which means the opening of esophageal tube is very small and narrow too small to support function.

complete failure leads to esophageal atresia

development of stomach

All about the formation of the greater and lesser curvature.

During the early 4th week the dorsal aorta is pushed into the dorsal abdominal wall and the celiac trunk is coming out of it. Stomach starts off as a fusiform shape with an edge extending ventrally and dorsally therefore the fusiform shape is along median plane. Dorsal border grows dorsally and ventral grows ventrally , the dorsal a little quicker and the ventral becomes lesser curvature and dorsal the greater curvature.

Stomach rotates 90 degrees clockwise using the initial tube as the point of rotation. Ventral border (lesser curvature) rotates to face right, Dorsal border (greater curvature) rotates to face left, Cranial region moves to left and inferior (on top), Caudal region moves to right and superior (at bottom)

At day 28 initially before stomach growth and rotation it is suspended in intraembryonic body cavity and suspended to dorsal abdominal wall by dorsal mesogastrium.

As stomach grows and rotates, dorsal mesogastrium spins with it so by day 48 what would have been the dorsal mesogastrium now has the pancreas and spleen growing within it. Looping occurs and this allows the double layer of peritoneum which extends from greater curvature (greater omentum)

Development of Liver and Gallbladder

Liver and gallbladder start as buds extending from the duodenum which extend ventrally and grow into the ventral mesogastrium. Primordial liver grows much faster than the gallbladder. The gallbladder ends up at the inferior pole of the liver. There are ducts from the liver called hepatic ducts that extend downwards and connect to the duct from the gall bladder and they drain together behind the stomach connecting to the duodenum. The pancreatic duct enters the duodenum at same level as hepatic and bile ducts at duodenal papilla.

Development of the Pancreas

Starts off as two buds, ventral one extending into ventral mesogastrium and dorsal one extending into dorsal mesogastrium. As the pancreatic buds grow in those two locations they end up being clusters of pancreatic tissue and as the stomach goes through its 90 degree rotation it will drag the ventral bud dorsally.

Before any spin, ventral pancreatic bud extends in opposite direction. As the stomach and duodenum spins the ventral bud is carried towards the dorsal bud and eventually will fuse together.

derivatives and blood supply of the midgut

derivatives:

- distal small intestine (duodenum, jejunum, ileum)

- proximal large intestine (cecum + appendix, ascending colon, right 2/3 of the transverse colon)

Supplied by the superior mesenteric artery

Development of the midgut

Midgut Loop Growth:

As midgut grows forms a ventral U shaped loop that is suspended from dorsal/posterior abdominal wall by mesentery proper. The midgut loop elongates through the abdomen into the proximal part of the cord at the beginning of the 6th week in a process called umbilical herniation. The Cranial limb grows rapidly forming intestinal loops and the caudal limb goes through very little change. These two limbs are separated by the omphaloenteric duct.

Rotation of midgut loop:

Cranial and caudal limbs rotate 90 degrees so they are next to each other and become rich and left. While the intestines are being brought back into the abdomen we continue the remaining 180 degrees so that the cecum and appendix are in the correct location in the lower right quadrant. Total rotation of 270 degrees counterclockwise. Everything rotates around the superior mesenteric artery, it serves as the axis.

Reduction of midgut hernia:

During the 10th week the small intestines return into the abdomen and take up most of the space so that when the large intestine returns it has to fill the borders of the abdomen

what is the omphaloenteric duct

connection from midgut through umbilical cord

Congenital Omphalocele

When midgut doesn't return to the abdomen, so the abdominal contents end up in the umbilical cord for too long. Unknown cause and affects 1/5000 births but half are stillborn.

Congenital ileal diverticulum (meckel diverticulum)

When the proximal part of the omphaloenteric duct (yolk stalk/vitelline duct) doesn't completely go away so there is a little bit left that can protrude outwards. Very harmless unless it gets infected and effects 2-4% of population.

Sometimes it maintains a connection to anterior body wall via fibrous cord that connects diverticulum to inside of umbilicus. If the cord isn't there and the lumen of the duct persists this is called the omphaloenteric fistula which causes fluid from intestines to leak through the belly button.

Derivatives and blood supply of the hindgut

derivatives:

- distal large intestine (left 1/3 of transverse colon, descending colon, sigmoid colon)

- rectum

- Superior anal canal

- Epithelium of urinary bladder and most of urethra.

supplied by inferior mesenteric artery

Development of the hindgut

All about the cloaca which is a space where hindgut and primordial bladder empty into. But in adult they don't empty into same holes so we need to separate the cloaca into two tube systems and this is called partitioning of cloaca.

Urorectal septum (mesoderm) grows in through cloaca which divides it into two tube systems (urogenital sinus - all about urinary system) and anorectal canal (which is end of hindgut)

With growth of the septum the cloacal membrane separates into urogenital membrane and an anal membrane, which eventually degenerate to form openings which open to exterior.

Upper and lower limb anatomy

upper limb:

-arm has humerus bone

- forearm has radius and ulna (radius towards thumb), the bones side by side

- carpal bones (wrist) 8 of them

- phalanges (bones of digits)

lower limb:

- main bone in stylopod is femur

- two parallel bones in zeugopod = tibia and fibula (tibia bigger and bulkier)

- torsals (7 of them)

- Phalanges (digits)

Axis of limbs

Proximodistal Axis: from point of attachment to tip of limb. Proximal is closer to point of attachment, distal is far away. This length makes limb longer.

Dorsoventral axis: extends from front of limb to back of limb. Comes out of page towards us. flexors are ventral, extensors are dorsal.

Craniocaudal axis: from cranial limb margin to caudal limb margin (thumb cranial, pinky caudal) limb becomes thicker along this axis.

Development and Growth of limb buds

Upper and lower limb buds emerge as anterolateral projections. The craniocaudal location of limb buds are determined by fibroblast growth factor gradient.

Initially the buds consist of mesenchyme from the somatic layer of the mesoderm which becomes bones and muscles of the limbs and on the outside of the limb buds ectoderm will form the skin of limb buds.

Cell derivatives within limb bud

Neural tube = motor nerve axons

Neural crest = Schwann cells, sensory nerve axons, melanocytes (skin pigment)

Somite = muscle, endothelial cells

lateral plate mesoderm = skeleton, connective tissue, blood vessels, muscles

What is the apex of the developing limb marked by?

a ridge of thickened ectoderm; appeal ectodermal ridge (AER)

AER

Found on edges of limb buds and promotes elongation through expression of FGFs (fibroblast growth factors. This works by it inducing adjacent mesenchyme (via FGF) to stay in a very proliferative state. This delineates a region called the progress zone which is the zone where the developing limb has lots of active cell division. As it elongates the progress zone leaves behind cells. Proximal cells become further and further from the progress zone because they are under less inductive signaling influence.

ZPA

Zone of polarizing activity and it is found at the caudal border and proximal border only on one side, so it is important in making sure the cranial and caudal elements (thumb and pinky) develop in right way

Proximodistal growth and differentiation (along transverse axis)

FGFs from the AER keep mesenchymal cells near distal tip of limb in a proliferative state, as you get more proximal FGF is more diffuse. Retinoic acid from the ZPA causes differentiation proximally, so as you move more distally it is more diffuse. This makes sure that areas can differentiate so that you can have a long limb with bones and muscles in the right area. Causes cells in the proximal area to differentiate from mesenchyme into bone and muscle. (proximal limb segments like stylopid differentiate first).

Finger and toe formation

By week 5 at the distal portion we have a plate forming (digital plate) and it differentiates forming fingers. The core of the actual plate condenses towards the end of development forming digital rays which are little segments representing underlying condensing mesenchymal tissue. These spaces in the digital rays go through apoptosis to form notches which continue to break down and form individual separate digits shedding the webbing.

Timeline for digital formation

Buds - hand and foot plates - digital rays - notches between rays - webbing - separate digits

upper limb: day 27 limb bud, day 32 paddle shaped plate, day 41 digital rays, day 46 notches between digital rays, day 50 webbed fingers, day 52 separate digits

lower limb: day 28 limb bud, day 36 paddle shaped plate, day 46 digital rays, day 49, notches between rays, day 52, webbed toes, day 56 separate digits.

foot progresses little later always a step behind

craniocaudal limb differentiation (along vertical axis)

As limb grows along transverse axis, ZPA starts off at the proximal aspect of limb development and grows with AER and ends up where wrist/ankle joint is. (proximodistal)

It controls craniocaudal differentiation through sonic hedgehog which makes sure the thumb is on the right side as well as pinky. If ZPA (which produces retinoic acid) was transplanted on other side the limb will have 2 areas secreting Shh and the gradient will be disrupted causing extra digits formed.

Digital Abnormalities

Polydactyly: presence of extra digits inherited as an autosomal dominant trait (not due to duplicated ZPA)

Syndactyly: presence of fused digits , most common is cutaneous syndactyly which results from failure of webbing to degenerate (overlying ectoderm does not properly undergo apoptosis. This is easy to fix just cut them and it heals.

Dorsoventral limb differentiation

Radical fridge (r-Fng) is secreted from the dorsal ectoderm, Engrailed 1 (En-1) is secreted from the ventral ectoderm. The AER is the border between dorsal and ventral limb bud ectoderms. This system ensures flexors and extensors end up on correct side

Positional changes of developing limbs

All limbs start identical in development and then upper limbs rotate externally (laterally) 90 degrees causing the elbow to point caudally and flexor muscles anterior, then the lower limbs rotate medially (internally) almost 90 degrees cause the knee to point cranially and the flexor muscles posterior

Formation of limb skeleton

Diaphysis of long bones - shaft and primary ossification center

Epiphysis of long bones - ends and secondary ossification centers

Epiphyseal cartilage plate - in between shaft and end (epiphyseal growth plate which does not fully ossify until each person completes puberty.

Early in limb development, mesenchyme condenses to produce blueprint of future bone development, no cartilage at this point.

During 6th week the mesenchymal blueprint in upper limb will undergo chondrification to form hyaline cartilage bone models and by the end of the 6th week (day 42) cartilaginous models of bones of upper limb are complete.

We then around day 56 (end of embryonic period) get ossification of limb long bones. The primary ossification centers form in center of diaphysis of long bones (humerus, radius, ulna)

BY 12th WEEK PRIMARY OSSIFICATION CENTERS FOUND IN ALL LIMB BONES

Secondary ossification centers for distal femur and proximal tibia are present at birth but all other secondary centers appear after birth

UPPER LIMBS DEVELOP BEFORE LOWER

Formation of limb musculature

Muscles develop as well as the bones. Migration of muscle progenitor cells enter anterior or posterior side of the bone. The centrally located bone has extensor muscles on one side and flexors on the other. The myogenic precursor cells migrate into the limb from nearby somites (most times) and nervous innervation from these muscles come from spinal cord (ventral primary ramus)

upper limb buds lie opposite to lower cervical and upper thoracic segments of somites. lower limb buds lie opposite to lower lumbar and upper sacral segments further down embryo.

Adult complete vertebrae

7 cervical (small and delicate) , 12 thoracic (articulate with ribs), 5 lumbar(weight bearing) , 5 sacral (fused so vertebrae fused together as one individual sacrum in triangular shape) , 3-5 coccygeal (vestigial)

anatomy of vertebrae

Hole in centre of every vertebrae called the vertebral canal where the spinal cord passes through and is protected by bony elements on all sides, the vertebral body and ventral arches. In every shape of vertebrae the vertebral body which is the weight bearing portion looks the same.

Extensions of bones from arch care called processes:

- bilateral transverse processes

- sinuous process which extends posteriorly in the adult

Vertebral arches form on either side and then fuse at spinuous process. So if there is improper fusion won't be properly protected.

Intervertebral discs

Composed of the annulus fibrosis and the nucleus pulposus.

Anulus fibrosis is the outer region that is fibrous, strong and sturdy.

Nucleus pulposus is the squishy centre , is the remnant of the notochord at each level. The notochord will extend all the way through the centre of the vertebral bodies , cells will aggregate around the notochord and differentiate into bone. The ones that don't turn into bone will be left behind as the nucleus pulposus.

Exceptions to normal vertebrae

C1 - atlas, C2 - axis, Sacrum.

Fate of mesoderm in the back

Somites form from within the mesoderm and form on either side of developing notochord in a craniocaudal direction. Starts mostly cranially and progress caudally.

Somitogenesis

As the primitive streak regresses caudally, it leaves in its wake the developing notochord. Cranial somitomeres form within the paraxial mesoderm on either side of the notochord. However cranial somitomeres do not become somites, instead they will become most of the skeletal musculature of the head. Caudal to the 7th pair of cranial somitomeres, the first pair of somites emerges from caudal somitomeres in the occipital region around day 20-30. Somites appear from this point caudally at a rate of about 3 somites/day. 42-44 pairs will develop in total (5 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 8-10 coccygeal.

the 1st occipital and last 5-7 coccygeal disappear and the remaining form the axial skeleton.

Somite Epithelialization

Epithelialization is where somites turn into epithelial cells. The mesenchymal cells cluster around themselves and form a ball which has a cavity in the center of it.

Ventral region:

the ventral region turns back into mesenchyme so all of the cells migrate. When they turn into mesenchyme they become sclerotomes and migrate ventrally and medially and proliferate. The sclerotomes on the right and left side fuse and surround the notochord and neural tube. Sclerotome goes on to form the vertebrae which makes sense that it migrates around the neural tube (spinal cord) and notochord (nucleus pulposus)

Dorsal region:

Breaks apart into dermatome and myotome. Dermatome is found between the elements that become myotome it forms elements like skin. The myotome forms muscle. Cells from the ventrolateral lips and dorsomedial lips transform back into mesenchyme and migrate beneath the dermatome and elongates.

lateral somitic frontier

It is a border between each somite and somatic (parietal) layer of lateral plate mesoderm. It separates the abaxial and primaxial domains.

Cells that cross the somitic frontier and are close to the lateral mesoderm form the abaxial domain and contribute to ribs and muscles, the somite muscle cells are able to cross over and be adjacent to lateral plate and can mix together to form different things. Those that don't cross turn into the primaxial domain and do not mix with lateral plate mesoderm so receive differentiation signals from medial structures.

Polarization

Notochord and neural tube (floor plate) secrete sonic hedgehog and noggin which causes the ventral region of the somite to form the sclerotome, which expresses PAX1 (which controls chondrogenesis and vertebrae formation.

Neural tube (dorsal part) secretes WNT proteins which causes the dorsomedial lip of the dorsal region of the somite to differentiate into primaxial muscle precursor cells and to express muscle specific gene MYF5

Dorsal part of the neural tube also secretes neurotrophin 3 (NT3) which causes the mid-dorsal portion of the somite to become the dermatome. The ectoderm overlying the ventrolateral lip secretes activating WNT proteins and lateral plate mesoderm secretes inhibitory BMP4 (bone morphogenic protein 4) which causes the ventrolateral lip of the dorsal region to express the muscle specific gene moD and to differentiate into both primaxial and abaxial muscle precursor cells.

vertebrae resegmentation

As sclerotome migrates around notochord/neural tube it goes through resegmentation. Each sclerotome gets divided into a cranial and caudal portion and migrate away from each other. Cranial portion of C2 will migrate towards its caudal portion of neighbor C1. Caudal portion of C2 goes toward cranial portion of C3.

Chondrification of vertebrae

Mesenchyme condenses to form cartilage then forms bone. Mesenchyme takes on general shape of a vertebrae with a vertical foramen in the centre. The centrum turns into the ventral body, costal processes turn into the transverse processes. Neural arch turns into vertebral arch and spinuous process. Within the mesenchyme are chondrification centers forming in the centrum and neural arch as well as close to the costal process. They turn mesenchyme into a cartilage blueprint which is later used to create bone.

DURING FIFTH WEEK

Ossification of vertebrae

First primary ossification center forms within the 7th week within the centrum. The primary ossification centers close to the costal processes don't come along until the 8th week. Once a baby is born they have not fully ossified all of the cartilage surrounding the posterior aspect , the vertebrae don't fully fuse until age of 25.

Hemivertebra

Normally 2 chondrification centers within the centrum. They make cartilage on either side of the notochord around the ventral body. If they don't fuse, this means the vertebral body will only form on one half resulting in hemivertibrae.

only half vertebral body forms which can cause entire column to bend a little which is a common cause in people with congenital scoliosis.

Formation of Back Musculature

Skeletal muscles derived from myotome part of somite. Ventrolateral and dorsomedial lips both contribute. Each developing spinal nerve divides the branches so that the dorsal primary ramus supplies the primaxial muscles of back like major back and neck extensors. The ventral primary ramus supplies muscles of lateral and anterior body walls and limbs.

primary neurulation

1) Induction of the neuroectoderm:

Notochord induces the overlying ectoderm to turn into the neural plate Which thickens forming neural folds on either side of the neural groove.

2) Elevation of neural folds:

Neural folds reach dorsally and then start to reach medially and eventually fuse together. Cell wedging happens at hinge points where cells look triangular with broad base and a narrow apex. The notochord controls position of median hinge point.

3) Conversion, Contact, and Fusion of the Neural Folds:

Neural tube has separated from overlying ectoderm and in between there are neural crest cells which are the tips of the neural folds. They migrate away and form a variety of different structures. We see fusion at the 5th somite, approximately between 4th and 6th. Once the neural tube closure happens at the cervical somite 4-6, it progresses cranially and caudally eventually closing the cranial and caudal neuropore (cranial closes at day 25, caudal at 28)

4) Delamination from the surface ectoderm:

The neural tube differentiates into the CNS (brain and spinal cord) and neural crest cells becomes most of PNS and ANS