Dev Bio Final

Identify the four main types of mesoderm

1. Chordamesoderm

2. Paraxial mesoderm

3. Intermediate mesoderm

4. Lateral plate mesoderm

Chordamesoderm

• forms the mesoderm

• most central

Paraxial mesoderm

• forms the somites; anteriormost paraxial mesoderm does not segment → becomes the head mesoderm

• on both side of the notochord

Intermediate mesoderm

• forms the urogenital system → kidneys and gonads

• directly lateral to paraxial mesoderm

Lateral plate mesoderm

• forms the heart, blood vessels, blood cells, linings of body cavity, pelvic and limb skeleton

• farthest from notochord

Somitogenesis

the formation of somites, involving the periodic creation of an epithelial block by the mesenchymal cells of the presomitic mesoderm

Pre-somitic mesoderm

• subset of paraxial mesoderm that is unsegmented and is located on each side of neural tube immediately behind the forming somites → precursor to somites

• segments periodically in an anterior to posterior manner to form somites

What happens to the number of somites as development proceeds?

number of somites increases

How are somites built?

• pre-somitic mesoderm only contains mesenchymal cells → mesenchymal to epithelial transition

• become a compact epithelial tissue as fibronectin matrix deposition seals the new somite outer wall to form somite block

• each somite separates from the pre-somitic mesoderm at the anterior end forming somite pairs

What are the 2 big questions regarding somitogenesis?

1. WHEN should a somite form → controlled by the clock

2. WHERE should the boundary form so somites are always the same size → controlled by wavefront

Describe the “clock and wavefront” model.
Describe the “clock and wavefront” model

In this model, two converging systems interact to regulate (1) where a boundary will be capable of forming (the wavefront) and (2) when epithelial boundary formation should occur (the clock).

Outline the clock and wavefront process

• wavefront (determination front) is established by gradient of antagonistic retinoic acid and FGF

  • RA is high in anterior and decreases posteriorly

  • FGF is high in posterior and decreases anteriorly

• high FGF signaling maintains PSM cells in immature state → cells that receive low RA and FGF concentration will become competent to form a boundary to create a somite

  • determination front is where RA and FGF overlap → cells are competent to Notch signaling to build somite

• cyclic expression (turn on + off in cycles) of Notch genes (Lfng, Hairy1) → Notch turns on these genes which are expressed throughout PSM from posterior to region last somite formed

• high Notch wave hits determination front to induce MET to create new somite boundary

Can cells form somites while exposed to high FGF?

NO

What happens if the clock is sped up?

formation of numerous, smaller somites

What happens if clock is slowed down?

formation of fewer, larger somites

Identify factors that influence somite identity/specification along the A-P axis

• as somites form they are exposed to different Hox gene combinations depending on their position along A-P axis

  • each somite receives unique Hox code

• specify somites to receive cervical, thoracic, lumbar, or sacral identities

What happens if Hox genes are not expressed in discrete regions?

overexpression leads to structural abnormalities

• e.g. if thoracic Hox gene expression expands into cervical region → cervical vertebrae may develop ribs

What are the cells the somites give rise to?

Somites are transient and as they mature they split into compartments that give rise to specific tissue lineages:

• sclerotome cells → contribute to cartilage

• syndetome cells → contribute to tendons

• myotome cells → contribute to skeletal muscle

• endothelial cells → contribute to dorsal aorta

• dermatome cells → contribute to dermis + skeletal muscle

Describe the different regions that the somite subdivides into

1. sclerotome: made up of migratory mesenchymal cells

2. dermomyotome: made up of remaining epithelial cells

How does the sclerotome region form?

EMT occurs in the ventromedial portion of the somite forming the sclerotome

Sclerotome cells give rise to

• vertebrae along A-P axis, cartilage, tendons, meninges of spinal cord

What cells are within the sclerotome (ventromedial) division of the somite?

• sclerotome cells

• syndetome cells

• endothelial cells

How does the dermomyotome form?

remaining epithelial structure in the dorsolateral region of the somites

• does NOT undergo EMT

What two regions in the dermomyotome subdivided into?

1. Dermatome → precursor to dermis of the skin

2. Myotome → skeletal muscle precursor

How is the myotome region formed?

myoblasts (muscle precursor cells) migrate beneath the dermomyotome to produce the myotome

What are the two myotome regions?

1. Primaxial myotome/muscle

2. Abaxial myotome/muscle

Primaxial myotome

• myoblasts in myotome closest to neural tube form the centrally located primaxial myotome

• gives rise to: intercostal muscles of the ribs + deep muscles of the back

Abaxial myotome

• myoblasts in the myotome farthest from the neural tube form the abaxial myotome

• give rise to: body wall, limbs, tongue

Define the paracrine factors that form the different regions of the somite

• Sclerotome: high Shh from floor plate + notochord

• Dermatome: Neurotrophin-3 + Wnt1 from dorsal neural tube

• Myotome:

  • Primaxial: low Shh, Wnt1 + Wnt3 from floor plate + notochord

  • Abaxial: BMP4 + Fgf5 from lateral plate mesoderm, Wnt from epidermis

Outline the process from somite to vertebrae formation

• notochord induces surrounding mesenchyme cells to secrete epimorphin

• epimorphin attracts sclerotome cells to region around notochord and neural tube where they condense and differentiate into cartilage

• as nerves from the spinal cord migrate they split the sclerotome into an anterior and posterior segment

• as motor neurons grow to innervate newly forming muscles the anterior segment of each sclerotome recombines with the posterior segment of the next anterior sclerotome to form new vertebrae → re-segmentation

Resegmentation

the primary segments established by somites reorganize by half a segment to form the definitive vertebral column

• by shifting the skeletal segments by half a unit, each muscle block (myotome) directly straddles an intervertebral joint

  • muscle anchors to two successive vertebrae, providing the leverage necessary for lateral bending and movement of the spine

Intermediate mesoderm

forms the urogenital system consisting of the kidneys, gonads, and their associated ducts and outer portion of adrenal gland

• located in trunk/posterior of body → in between paraxial and lateral plate mesoderm

Describe how scientists determined how location of the intermediate mesoderm was important for kidney induction

• scientists separated intermediate mesoderm from paraxial mesoderm

• intermediate mesoderm couldn’t turn on

  • determined that intermediate mesoderm must have contact with paraxial mesoderm to form kidneys

What are the 3 stages of mammalian kidney development

1. Pronephros → transient in humans; fish/amphibian larvae gain functional kidney at this stage

2. Mesonephros → transient

3. Metanephros → mammals get functional kidney at this stage

Pronephros

• pronephric duct arises in intermediate mesoderm ventrolateral to anterior somites

  • cells migrate caudally and anterior region of duct induces adjacent mesenchyme to form pronephros of developing kidney

• in mammals, pronephros degenerate but more caudal portions of pronephric duct persist to become nephric duct

  • central component of excretory system

Mesonephros

• nephric duct induces adjacent mesenchyme to form mesonephros

  • as more tubules are induced caudally the anterior mesonephric tubules begin to regress through apoptosis

• mesonephros is the main source for hematopoietic stem cells necessary for blood cell development; some become epididymis and vas deferens in males

Metanephros

• permanent kidney of amniotes

• formed through reciprocal induction between ureteric bud and metanephrogenic mesenchyme

Describe the use of reciprocal induction during kidney development

• kidney is formed from 2 intermediate mesoderm populations:

  • ureteric bud and metanephrogenic mesenchyme

• metanephrogenic mesenchyme becomes committed in posterior regions of intermediate mesoderm where it induces epithelium of ureteric bud to branch from each paired nephric duct

  • forms collecting ducts and ureters

• when ureteric buds emerge from nephric ducts they enter the metanephrogenic mesenchyme where the epithelium at the tips of the branches induces the mesenchyme to aggregate

  • forms the nephrons and tubules through division

Explain how paracrine factors are critical for reciprocal induction

• Wnt9 and Wnt6 are released from ureteric bud to induce the surrounding metanephorgenic mesenchyme to form the tubular epithelium (nephrons)

  • these paracrine factors induce Wnt4 which acts in an autocrine manner to complete MET transition

Explain bladder development and kidney connection

• initially ureter empties into a cloaca which is lined by endoderm

  • maintained in adult birds, reptiles, amphibians and functions as waste receptacle for both intestine and kidney

• in mammals, a urogenital septum forms separating the rectum from the urogenital sinus → forming the bladder

Cloaca

a single rear opening that serves as the common chamber for intestinal, urinary, and reproductive tracts replacing separate urinary and anal openings

Lateral plate mesoderm

forms the circulatory system consisting of the heart, blood cells, and blood vessels

• located on the lateral side of each of the two bands of intermediate mesoderm

What does the lateral plate mesoderm subdivide into?

1. somatic mesoderm (body cavity) → dorsal layer

2. splanchnic mesoderm (circulatory system) → ventral layer

What is the space between the two layers?

coelom → becomes the body cavity by stretching from the future neck region to the posterior of the body

What does the somatic mesoderm divide into

somatic mesoderm underlies the ectoderm → together form the somatopleure

What does the somatopleure give rise to?

• limb bones

• pelvis

What does the splanchnic mesoderm divide into?

splanchnic mesoderm overlies the endoderm → together form the splanchnopleure

What does the splanchnopleure give rise to?

• circulatory system

What does the coelom divide into?

• pleural cavity → space surrounding thorax

• pericardial cavity → space surrounding heart

• peritoneal cavity → space surrounding abdomen

What is the first functional organ in the body?

the heart

How are the heart fields formed?

• vertebrate heart arises from two regions of splanchnic mesoderm—one on each side of the body—that interact with adjacent tissue to become specified for heart development

  • cardiogenic mesoderm are cells within the heart field that form the heart

• heart field is divided into 2 regions:

  • first field: progenitor cells form the primary heart tube but these cells have limited proliferative ability and will generate only the major portion of the left ventricle

  • second field: progenitor cells add cells to both anterior and posterior of heart tube → produce atria at posterior end and produce right ventricle and outflow tracts at anterior end

What are the cell types of the heart generated from the heart fields?

• Endocardial endothelial cells: line/cushion the heart

• Atrial myocyte: fill in atrial cavity to give musculature

• Ventricular myocyte: muscle or Purkinje fibers that coordinate heartbeat

Describe the key signals that are needed to specify the cardiogenic vs hemangiogenic mesoderm

• Cardiogenic mesoderm:

  • cells near anterior of body do not receive Wnt → blocked by inhibitors secreted by anterior endoderm

  • cells receive BMP + Fgf8 to convert LPM into cardiogenic mesoderm

• Hemangiogenic mesoderm:

  • cells near posterior of body receive Wnt signals

  • converts LPM into hemangiogenic mesoderm

• In the center of the embryo Noggin + Chordin signals from the notochord block BMP → cardiogenic + hemangiogenic fields do not form in the center of the embryo

Cardiogenic mesoderm

Precursor to the heart fields

Hemangiogenic mesoderm

Precursor to blood, blood vessels

Describe the process of heart tube formation starting with cardiogenic mesoderm and finishing with a single tube

• cardiogenic mesoderm cells migrate from splanchnopleure creating two populations:

  • one on the right + left side of the neural tube

  • each side has its own first and second heart fields → each side forms its own heart tube

• two endocardial tubes form that migrate and fuse together to create one heart tube

What happens if the two heart tubes fails to migrate and fuse?

Cardia bifida: two separate hearts form, one on each side of the body

• cannot sustain life

How is the heart formed?

• formation of the foregut allows for formation of single tube

• final endocardial tube consists of:

  • endocardium surrounded by myocardium (muscle)

Describe the process of heart looping

• at 21 days of development the human heart is a single chamber tube → must loop to become a two chambered tube: atrium to receive blood and ventricle to pump blood out

• pressure from blood flow helps drive looping to completion

• when looping is complete portion of the heart tube destined to become the atria lies anterior to the portion that becomes ventricles

• the septa forms from migrating cardiac neural crest cells

What does the heart need in order to pump blood after it has formed?

vascular system must establish its circulatory loops → blood vessels

Outline vasculogenesis

network of blood vessels is created from scratch from the splanchnic mesoderm of the lateral plate

• combination of BMP, Wnt, and Notch signaling activates Etv2 transcritption factor in LPM cells converting them to hemangioblasts

• Low Notch signaling causes hemangioblasts to become endothelial (blood vessels)

• High Notch signaling causes hemangioblasts to become blood cells

Outline angiogenesis

blood vessel network is remodeled into veins, arteries, and capillaries

What are the sites of vasculogenesis?

• In amniotes, extraembryonic vasculogenesis occurs in “blood islands” of the yolk sac

  • formed by the hemangioblasts and give rise to early vasculature needed to feed the embryo

• intraembryonic vasculogenesis forms the dorsal aorta