Embryonic Development

Embryonic Genetics

Cell Diferentiation and
Transcription Factors

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  • transcription factors determine the differentiation of a cell

*Organ Embryology

*Pancreas and Pancreatic Buds

*Sexual Organ Development

External Genitalia Differentiation (M vs F)

  • comes from abnormal migration of the ventral pancreatic bud

Case presentation:

Notes:

  • hypospadius = "below the tear"
  • hypospadias in males refers to the non fusing of the urethral / urogenital folds that equally in female counterpart stay open to form the labia minor of the vagina oriface
  • in men the urogenital folds close to form the penile raphe = the fold of skin that goes all the way from the anus and perineum to the glans of the penis
  • hypospadius results in the urethra opening prematurely before the glans --> hence hypo spadius = tear or openning

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3 Primary Germ Layers

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*Bladder and Urinary tract

Allantois Remnant = Urachus

Case presentation:

Notes:

  • the urachus / allantois during fetal development connect the urogenital system to the yolk sac
    --> through the umbilicus
  • this is meant to obliterate, but if it doesn't then the child will have leakage of urine through the umbilicus

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*GI tract Embryology and Disorders

Hirschprung Disease

  • failure of neural crest cells to migrate caudally to form the myenteric plexus
  • results in megacolon

Notes:

  • Rostral vs Caudal migration of embryology cells
    --> neural crest cells are caudal migration cells when they develop into enterocytes and the Glial cells of the periphery that make up the enteric plexus needed for peristalsis
  • in the question above you need to knwo they migrate in a caudal fashion, so in H disease the colon is always affected
  • depending on when the Neural crest cells stopped migrating the absence of myenteric plexus formation starts at the rectum and goes rostral direction, like in Ulcerative Colitis
  • key presentation for Hirschprung disease is
    --> failure of infant to pass meconium in forst 48 hours
    --> since the end of the colon essentially won't move
  • they also have symptoms of BO
    --> emesis (bilious), abdominal distension

Case presentation:

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*Face Development

  • Cleft Palate Deformity

Cleft Palate Deformity example

Case presentation:

Notes:

  • note from the anatomy to the right, the Volmer is the middle bone in the septum and the maillary bones are the bones that join above the mouth
    --> failure of the intermaxillary segment predominances is what causes cleft palate
  • Normal face development picture to the right
  • during 5th 6th week of embryo developemtn
  • the 1st pharyngeal pouch diveds into the 2 bone segments above and below that make up the mouth
    --> upper = maxillary
    --> lower = mandible
  • first the 2 medial nasal prominances have to fuse to make the intermaxillary segment
    --> the intermaxillary segment becomes the ANCHOR of the upper lip
    --> note this is counterintuitive since the intermaxillary segment doesn't come from the maxillary, but from the nasal and forms the anchor or backbone for the lip to form in front of it

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Unilateral vs Bilateral Cleft palate

  • need the 2 medial nasal segements to fuse
    --> these form the anchor and backbone of the palate and upper lip
  • the left and right maxillary segments then need to come to the middle and attach to the anchor
  • if one of these fail to attach tot he intermax then you get unilateral cleft palate

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Cleft Lip vs. Cleft Palate

  • note that you can get cleft lip +/- cleft palate and vice versa
  • it can also be a cleft of the entire palate or just the anterior part

*Internal Genitalia Development

Male internal and external sexual Organs

  • Leydig and Sertoli cells, and SRY gene on the Y chromosome

Case presentation:

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Pharyngeal and Aortic Arches and Pouches

Notes:

  • note that SRY gene on the Y chromosome is what differentiates the undetermined internal gonads to become either testes or ovaries
    --> note that the default for everything is female
    --> so if there is no SRY gene on the Y chromosome then the gonads become ovaries
    • Leydig cells produce and secrete testosterone
      --> they give men a "Leg up in competition" = testosterone
  • Sertoli Cells "make certain the testosterone gets used" = they produce aBP = adrogen binding protein in order for DHT to bind in seminiferous tubules --> for semen
  • note that the Leydig cells and testosterone are what are responsible for making the rest of the internal genitalia and the external genitalia
  • internal male genitalia = testes (SRY gene Y chromosome), epididymis + vas deferens (Leydig and testosterone)
  • DHT make the penis and the prostate
  • note that while the external male genitalia comes from the Leydig cells and testosterone, the Mullerian develops into the female internal vagina and uterus
  • think the Mullerian duct MUST be taken out
  • it is the job of the sertoli cells to secrete AMH = anti Mullerian hormone to destroy it
  • in this case with correct Leydig but Sertoli inactive --> there is no AMH so you get both male and female internal organs, ONLY male external organs

Mullerian and Wolfian Ducts

  • Mullurian duct = vagina and others
  • Wolfian duct = epidimis and vas def

Mullerian Aplasia

  • short or absent vagina
  • no uterus
  • all external female characteristics normal

Case presentation:

Notes:

  • hypospadius = "below the tear"
  • hypospadias in males refers to the non fusing of the urethral / urogenital folds that equally in female counterpart stay open to form the labia minor of the vagina oriface
  • in men the urogenital folds close to form the penile raphe = the fold of skin that goes all the way from the anus and perineum to the glans of the penis
  • hypospadius results in the urethra opening prematurely before the glans --> hence hypo spadius = tear or openning

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Notes:

  • start with undifferentiated gonads
  • note that the Wolfian duct passively dies
    --> think women are more passive and just let it die because no Testosterone
  • in males the MUllerin duct is actively killed off by AMH = anti Mullerian hormone
    --> think males are more aggressive and want to kill things

*Brain Embryonic Development

HPE = Holoproencephalon

  • developmental field defect
  • means that one mutation or change leads to many others in development

HPE = Holoproencephalon example

Notes:

  • note that HPE presents with classic signs of closely set eyes, cleft palate
  • it is often caused by trisomy 21
  • it can also be caused by fetal alcohol syndrome

Case presentation:

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HPE Presentation

  • can present with cleft palate or porboscis
  • proboscis = missing nose or a nose in the form of a proboscis (a tubular appendage) located above the eye
  • note in animals the correct term for something like an elephants snout is a proboscis
  • nose of a mammal, especially when it is long and mobile such as the trunk of an elephant or the snout of a tapir.

*Heart and CVS
Embryological development

Heart Development

TGA = transposition of the Great Arteries

  • failure of the normal spiralling of the pulmonary and aortic trunk in development of the heart vessels

Notes:

  • note that failure of spiralling in the aorta and pulmonary trunk results in TGA
  • TGA = transposition of the great arteries
  • aorta connects to the right V and pulmonary trunk connects to the left trunk
  • TGA is not compatable with life
    --> needs surgery to switch them
  • only way infants live for a few days is if they have a PDA that allow blood to go between the trunk and the aorta

Case presentation:

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Development of Fetus Timeline

Days 1-7

Days 6-7

  • Blastocyst Implantation to Endometrium

Day 8

  • Blastocyst starts producing Beta hCG
  • think of Beta = 8 hCG

Week 2 Gestation

  • blastocyst embedding into the endometrium
    --> 2 weeks = Bi = Blast

Blastocyst

  • Blastocyst made of 2 parts: TROPH EEEE blast
    --> winning a TROPH EEEE is a BLAST
  • outer ring = trophoblast
  • inner line = embryoblast

Trophoblast

  • outer trophy of Blastocyst

Embryoblast

  • inner line = embryoblast
    --> becomes the embryo and fetus

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Amnion and Yolk Sac

  • EMBRYONIC DISK

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Trophoblast --> Chorion Formation

Week 3 Gestation = Yolk Sac splits into Vitiline --> Gut Tube + Allantois

  • Allantois = fake urethra
  • gut tube = looks like shrimp with amniotic sac
    --> starting to elongate like a fetus now

Weeks 4 -8 =
1 = Chorion + Amnion --> form Amniotic Sac
2 = Umbillicus Formation = from Vitilline duct + allantois + body stalk

  • Amniotic Sac = main job is to insulate and protect fetus

2nd Trimester
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3rd Trimester
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Chorion

Gut Tube

  • Vitelline duct
  • Gut tube
  • Allantois

1 = Amnioric Sac

  • formed from chorion and Amnion

Chorion

Surfactant production

  • begins sharply at 30 weeks gestation

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2 = Umbillicus Formation = from Vitilline duct + allantois + body stalk

  • Umbullicus = AV Body
    --> allantois + Vitlline + body stalk

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Weeks 2 - 8 Overview = 4 main membranes formed

  • Embryo body + Gut tube
  • Amniotic Sac
    --> Chorion makes both the placenta (fetal part) plus combines with amnion = Amniotic Sac
  • Placenta
    --> Chorion makes both the placenta (fetal part) plus combines with amnion = Amniotic Sac
  • Umbilical Cord

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Reproductive System Embryology

Conception --> week 5
= identical sexual development of embryo

Week 5 -6

  • Germ cells develop from yolk sac
  • Migrate from yolk sac --> nephrogenic part of Mesoderm

WEEK 7 = GONAD differentiation (M / F)

  • SRY gene = sex determining region gene on Y chromosome
  • if NO SRY gene --> default = female gonad production

Gonads

  • come from the mesoderm
  • meoderm = MEANS O DERM
    --> MEANS for GENES
  • gonads come from nephrogenic cord of the mesoderm

Week 5 Gestation Embryo

  • made of primary 3 Germ Layers
  • reason why it is not different sexually

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3 Priumary Germ Layers

  • Ectoderm
    --> Attractoderm
  • Mesoderm
    --> MEANS O DERM
  • Endoderm
    --> Endernal organ

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GREAT Gonad MIGRATION

  • week 5-6 of gestation
  • germ cells actually first start in the yolk sac
  • they migrate along the vitilline duct to the nephrogenic part of the mesoderm
    --> form the gonads from here

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Week 7 Gonad Differentiation = Male

Week 7 Gonad Differentiation = Male = testes formation

  • Seminiferus tubules

Week 8 = Sertoli and Leydig Cells

  • Leydig make testosterone
    --> active destruction of the Mullerian Duct
  • Sertoli cells make AMH
    --> AMH = anti-Mullerian Hormone

Mesonephric Duct = Wolffian Duc

  • also active degeneration of the paramesonephric = Mullerian Duct = female
  • done by Sertoli cells --> AMH

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Chorion

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Chorion

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Chorion

Week 7 Gonad Differentiation = Female

Week 7 Gonad Differentiation = Female = primordial follicles

  • primordial follicles = means the follicle germ cells make oocytes that dont complete meiosis 1 (stay in prophaase till puberty)

Paramesonephric Duct = Mullerian Duc

  • also passive degeneration of the mesonephric = Wolffian Duct = male

Paramesonephric Duct = Undifferentiated
--> NO SRY ==> Mullerian Duct

  • paramesonephric
    --> parameso = beside/lesser than meso = women
    --> nephric = because the gonads come from NEPHRO genic mart of meansoderm

Oogenesis in Ovaries

see notes above

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Chorion

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Chorion

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Chorion

Sertoli and Leydig Cells

  • Leydig make testosterone
    --> testosterone makes the rest of internal reproductive tract
    = epidydimis + vas deferens
  • think of the Leydig as LA DIGS = ALWAYS CREATING
    --> Leydig cells make testosterone
    --> in reproductive development testost MAKES Wolfian duct
    --> in adult life testost makes sperm cells
  • Sertoli cells make AMH
    --> note that testost already negative feeds back on LH
  • Sertoli cells in contrast to Leydigs that CREATE, Sertoli cells DESTROY
    --> in development they make AMH
    --> destroys the Mullerian duct
    --> in adult life the Sertoli cells make inhibin
    --> inhibin negative feeds back on FSH

Primordial follicles

SRY gene

  • makes testes determining factor

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Seminiferous tubules

  • note the seminiferous tubules contain spermatagonia
  • the spermatagonia though lay dormant until puberty
  • during puberty they then make sperm

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Undifferentiated Mesonephric and Paramesonephric Ducts

  • Mesonephric Ducts
    --> matures into male Wolffian Duct
  • Paramesonephric Ducts
    --> matures into f emale Mullerian Duct

Notes:

  • start with undifferentiated gonads
  • note that the Wolfian duct passively dies
    --> think women are more passive and just let it die because no Testosterone
  • in males the MUllerin duct is actively killed off by AMH = anti Mullerian hormone
    --> think males are more aggressive and want to kill things

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Mesonephric Duct = Undifferentiated
--> SRY ==> Wolffian Duct

  • mesonephric
    --> meso = main = man /
    --> parameso = beside/lesser than meso = women
    --> nephric = because the gonads come from NEPHRO genic mart of meansoderm

WEEK 9 = External Genitalia Differentiation

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Mesonephric Duct = Undifferentiated
--> SRY ==> Wolffian Duct

  • mesonephric
    --> meso = main = man /
    --> parameso = beside/lesser than meso = women
    --> nephric = because the gonads come from NEPHRO genic mart of meansoderm

Paramesonephric Duct = Undifferentiated
--> NO SRY ==> Mullerian Duct

  • paramesonephric
    --> parameso = beside/lesser than meso = women
    --> nephric = because the gonads come from NEPHRO genic mart of meansoderm

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Mullerian and Wolfian Ducts Case examples

  • Mullurian duct = vagina and others
  • Wolfian duct = epidimis and vas def

Mullerian Aplasia

  • short or absent vagina
  • no uterus
  • all external female characteristics normal

Case presentation:

Notes:

  • hypospadius = "below the tear"
  • hypospadias in males refers to the non fusing of the urethral / urogenital folds that equally in female counterpart stay open to form the labia minor of the vagina oriface
  • in men the urogenital folds close to form the penile raphe = the fold of skin that goes all the way from the anus and perineum to the glans of the penis
  • hypospadius results in the urethra opening prematurely before the glans --> hence hypo spadius = tear or openning

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Primary / Secondary OOcytes / Meiosis 1 and 2 Arresting stages

  • meiosis arrest #1 - begins at puberty
    --> PUBERTY = prophase of Meiosis 1
  • meiosis arrest #2 - begins at ovulation and fertilization
    --> ends at fertilization
    --> fertilization needs a MALE = metaphase of Meiosis 1

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Primary / Secondary OOcytes / Meiosis 1 and 2 Arresting stages CASE 1

  • arrest #1 - begins at puberty
  • arrest #2 - begins at ovulation
    --> ends after fertilization

Notes:

  • note that oocyte primary and secondary and meiosis is all happenning to the oocytes
  • these are within the follicles that contain the oocytes and feed them
  • thus the FSH growth of follicle and LH surge are happenning continuously each month while the oocytes are arrested in Meiosis prophase 1 = puberty state

Clinical Case

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Notes:


  • Gestation = mitosis of oogonium
  • Birth = start making Primary OOcytes from the oogonium
  • Childhood to puberty = Meiosis 1 prophase
    --> think PUBERTY = PROPHASE 1
  • MONTHLY MENSTRUATION = meiosis 1 complete / METAPHASE 2 arrest
  • Metaphase 2 arrest = until MEN arrive
    --> once sperm fertilize the metaphase 2 and entire meiosis 2 completes

External Genitalia Differentiation

WEEK 9 = External Genitalia Differentiation

  • either by testosterone or estrogen

Week 7 External Genitalia Differentiation = Male

Week 7 External Genitalia Differentiation = Female

ABSENCE of Testosterone

Undifferentiated External Genitalia

.

Testosterone --> 5-alpha - reductase --> DHT

  • DHT responsible for male external genitals

Urethral folds

  • fuse to form the body of the penis
  • in females the urethral folds are equivalent to the labia minora
  • labia minora = unfused urethral foldds

Initial Undifferentiated External Genitalia

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Urethral folds

  • in males fuse to form the body of the penis
  • in females the urethral folds are equivalent to the labia minora
  • labia minora = unfused urethral foldds

Scrotal swellings

  • in males form the scrotum
  • in females the Scrotal swellings = laboa majora are equivalent to the scrotum

Primordial Phallus

  • in males form the glans of the penis
  • in females forms the clitoris

WEEK 12 - Differentiation and external genitalia complete

  • reason why we do ultrasound at week 12
  • think of the clock = 12 hours = MIDNIGHT = turn into a PUMPKIN
  • tell the sex of the fetus

Week 12 Ultrasound = Males vs Female

WEEK 12 --> Birth = Descent of the Gonads (Female)

  • Shortenning the Gubernaculum

Gubernaculum

  • in females instead of becoming the spermatic cord, it splits into two ligaments that hold both the uterus and the ovaries
  • Gubernaculum splits --> Ovarian ligament + round ligament

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Chorion

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Chorion

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Chorion

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WEEK 12 --> Birth = Descent of the Gonads

  • Shortenning the Gubernaculum

Gubernaculum

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Chorion

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Chorion

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Chorion

Testicular Cord

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SUMMARY = External Genitalia Differentiation

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Lateral and Vertical Fusion of the Mullerian Ducts = Paramesonephric Ducts

  • can be seen on a HSG = hysterosalpingogram

Case presentation:

Notes:
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HSG = hysterosalpingogram

  • showing non lateral fusion of the Mullerian Ducts = Paramesonephric Ducts with the uterus

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Congenital Uterine Abnormalities

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*Kidney Embryonic Development

  • 3 main structures (similar to brain names = pro and meso)
  • pronephros
  • mesonephros
  • metanephros

-along with the 3 main nephros parts, starting at the COLLECTING DUCTS, the rest of the ureters are made from the

  • ureteric bud

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hCG Production

hCG Production case

Clinical Case

Notes:

  • note that the egg enters the uterus by day 3-4

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Chorion

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*Aortic Arches

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Notes:

  • first = maximal = maxillary artery
  • second = stapedus and hyoid
  • third = C = common carotid and proximal internal carotid
  • fourth = 4 limbs of systemic arteries
    --> the aortic arch between 2 left branch
    --> the bifurcation = proximal part of right subclavian artery
  • 6 = P upside down = pulmonary artery bifurcation + pulmonary to aorta shunt = ductus arteriosis

Aortic Arches case

Clinical Case

Notes:

  • note that

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*Blood Vessel Embryology

  • 3 main blood vesels in Embryo
    --> 2 remain as the systemic and portal vein system
    --> 1 dies off

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*Embryo Blood Vessel Derivatives

  • umbilical vein = degenerate into --> round ligment
  • vitilline veins --> portal system
    --> recall vitilline duct with the allantois forms the umbilical cord and degenerates after
  • cardinal veins --> system veins

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Deveiations from the normal Ventral wrapping around to unite with Dorsal pancreatic bud

  • rememebr the ventral does all the wrapping and migrating
    --> just like the trigger of a gun does all the work

Annular Pancreas

  • comes from abnormal migration of the ventral pancreatic bud

Notes:

  • annular pancreatis is the formation of annular ring of the ventral pancreatic bud that can constrict the duodenum
    --> reason why patients present with emesis and pancreatitis
  • note that the pancreas is part of SAD PUCKER = retro peritoneal
    --> except the tail of the pancreas
    --> this makes sense as the dorsal bud of the pancreas is dorsal or "behind"
    --> remember counter intuitive that the tail is the only thing retro peritoneal
    --> think of a gun being pulled at your back and shooting forward to the spleen
  • most annular pancreas are assymptomatic

Case presentation:

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Pancreatic Divisum

  • where the ventral pancreatic bud winds and migrates to dorsum bud
  • but they stay divided into separate buds = DIVISUM
  • thus the main pancreatic duct that normally comes from anterior bud can't go up to the body and tail
  • get 2 separate ducts

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*Testes Development and Descent

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Complications from patent process vaginalis

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Hydrocele

  • can be either communicating = patent process vaginalis
  • non-communicating (usually self-limiting?)

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*Ectoderm

  • "attract - o - derm"
  • things women care about
    --> hair, nails, skin = epidermis
    --> eyes - retina and lens
    --> brains = nervous system

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Mesoderm

  • "means - o - derm"
  • provides MEANS for genes (passing them on) and walking, and chili / kidney beans
  • MEANS for WALKING in JEANS = GENES
    --> skeletal and circulatory system
  • MEANS for GENES
    --> gonad development (from nephrogenic duct of meansoderm)
  • MEANS for kidney BEANS
    --> ALL Kidney shaped organs
    --> spleen, kidneys (+ ureters only) and adrenal glands
  • does NOT include the END tube organs

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Endoderm

  • "endernal organs"
  • ALL "END tubes from mouth to anus"
    --> lungs
    --> entire GI + accessory organs
    --> bladder + urethra

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*Umbilical Chord

  • UMVilical chord (in Irish) = Urachus + Meckel's / Vitilline

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Notes:
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Pharyngeal and Aortic Arches

  • First is MAXIMAL / 3 M bones and nerve
    Second is Stapedius artery / bone / Facial nerve
  • Third is 3rd in the alphabet = C = common carotid arteries

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Clinical Cases

Clinical Case

Clinical Case

Notes:

  • note that

Pharyngeal and Aortic Arches

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Mnemonic for Embryological aortic arches:

  • First is MAXIMAL
  • Second is Stapedius artery
  • Third is 3rd in the alphabet = C = common carotid arteries

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Pharyngeal Pouches

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Clinical Cases

Clinical Case

Clinical Case

Notes:

  • note that

Pharyngeal Pouches

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Notes:
for pharyngeal pouches

  • Third 3 = pharyngeal pouch
    --> Thymus and P thyroid (inferior and closest)
    --> note the THYROID gland does not come from the pharyngeal pouches, it comes from the GI pouches
  • the inferior parathyroid and thymus come from the THIRD pharyngeal pouch

AP TIPS at the sPUB
--> pharyngeal pouches give tips on ordering APPS at the PUB


1st pouch = A
--> auditory tube


2nd pouch = P
--> palantine


Third pouch = TIP
--> thymus / inferior parathyroid


1st pouch = sPUB
--> superior parathyroid / Ultimobranchial body

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Clinical Cases

Clinical Case

Notes:

  • note that

Clinical Case

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Clinical Cases

Clinical Case

Notes:

  • note that

Clinical Case

Embryonic development of the True Kidney example

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Case presentation:

Notes:

  • note that the true kidney comes from the metanephric part of the embryo
  • the ureteric bud develops everything distal in the kidney to the COLLECTING DUCTS

Fetal Hydronephrosis and Ureter Pelvic Junction = UPJ

  • UPJ is the last thing in the kideny ureter bladder to cannulize
  • can obstruct the ureter and give hydronephrosis

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*Neural Crest Cell Derivatives

  • Neural Crest GAMES

Neural Crest Cell Derivatives
example

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Notes:

  • note that cummulative incidence is over a specified time period like a year in this example
  • it does NOT count the people in the population who already have the disease so you have to subtract them from the total population first
  • you don't subtract anything else, even deaths since these people may have gotten the disease in the time period

Example:

Wear your home team CREST to the GAMES
... (AM go together)

  • think neural crest cells from 2 sides of nural tube
  • 2 letters for each
    G = glial cells (peripheral) / ganglia
    A = Arachnoid and pia layers / Adrenal Medulla
    M = medulla / melanocytes
    E = enterocytes / endocardial cushions
         --> End Cushions = (bed GAMES) 
         --> rest of Heart = (MEANS = Meso for living) 
    
    S = Schwann Cells / Skull bones

*Neural Tube of the Attractoderm

  • "NEURETINAL TUBE"
  • "NEURETINAL" = retinas
  • "TUBE " = brain
    --> behind the SURFACE Attractoderm (lens and cornea of eyes)
  • the TUBE is BEHIND the surface attractoderm
    --> has the post pituitary gland also

think of the brain as a TUBE behind the SURFACE Attractoderm

  • tube = brain and spinal chord
  • behind the SURFACE attractoderm
    = retina of the eyes and posterior pituitary gland

*Surface Ectoderm = Attractoderm

  • SURFACE of the eyes = lens + cornea
  • SURFACE of the pituitary gland = anterior pituitary gland

SURFACE of attractoderm

  • SURFACE of the eyes = lens + cornea
  • SURFACE of the pituitary gland = anterior pituitary gland

Clinical Cases

Clinical Case

Clinical Case

Notes:

  • note that

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*Home

Fetal *Circulation

Remnants of fetal circulation bypass arteries/veins

  • ductus venosis --> ligamentum teres (of liver)
  • foreman ovale --> fossa ovalis
  • ductus arteriosis --> ligamentum arteriosum

Fetal Circulation case

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Clinical Case

Notes:

  • anything going to the heart is a vein and anything away is an artery
  • recall the 3 areas of bypassing in the fetal circulation
  • ductus venosis
    --> umbilical vein bypasses the liver and portal system for the IVC
  • foreman ovale
    --> bypasses the right V and pulmonary system to go into the left atrium
  • ductus arteriosis
    --> from pulmonary artery bifurcation to the descending aorta to bypass lungs and left side of heart
   - Heart derived from

--> End Cushions = (bed GAMES)
--> rest of Heart = (MEANS = Meso for living)

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MEANS to hear

  • tympanic membrane = ear drum
    --> comes from ALL three layers
  • but the malleus, incus and stapes are bones
    --> thus come from the MEANSoderm
    --> Malleus = max arch = arch1
    --> stapes = secondar arch of mesoderm

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