Midterm Review Lecture Flashcards by Aubrey Hite

During what period of time is the central nervous system most sensitive to teratogens? What types of defects/abn?

3.5-beginning 6th

NTDs and intellectual disability

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During what period of time is the heart most sensitive to teratogens? What types of defects/abn?

4th week-end of 6th

TA, ASD, VSD

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During what period of time are the ears most sensitive to teratogens? What types of defects/abn?

end of 4th week-9.5

low-set malformed ears and deafness

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During what period of time are the eyes most sensitive to teratogens? What types of defects/abn?

5th-8.5

cataracts, glaucoma, microphthalmia

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During what period of time are the arms and legs most sensitive to teratogens? What types of defects/abn?

5th-7th

amelia/meromelia

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During what period of time are the teeth most sensitive to teratogens? What types of defects/abn?

beginning of 7th-end of 9th

enamel hypoplasia and staining

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During what period of time is the palate most sensitive to teratogens? What types of defects/abn?

beginning of 7th-beginning of 9th

cleft palate

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During what period of time are the external genitalia most sensitive to teratogens? What types of defects/abn?

end of 7th-end of 9th

masculinization of female genitalia

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What is happening in week 1 of development?

Day 1 - fertilization
Day 2 - 2 cells
Day 3 - morula (16 cells)
Days 4-5 - early blastocyst
*embyroblast, trophoblasts, blastocyst cavity
Day 6 - implantation starts to happen (trophoblasts differentiate)

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What is happening in week 2?

Week of 2s
Day 8 - Embryoblast differentiates
Hypoblast: surrounds primitive yolk sac, Epiblast: becomes trilaminar disc
Amniotic cavity forms

Day 9 - you have two layers of trophoblast, two layers of embryoblast, amniotic cavity and primitive yolk sac, Syncytiotrophoblast develops lacunae (premature chorionic villi), Implantation complete, Primary yolk sac formed

Day 11 - primary villi begin to form (syncytiotrophoblasts invade lacunae/maternal sinusoids)

Day 12 -
Syncytiotrophoblast invades maternal sinusoids
Secondary yolk sac formed
Extraembryonic mesoderm differentiate
1.Parietal/somatic: body cavity, pelvis, limb bones, etc.
2.Visceral/splanchnic: circulatory system

Day 13 - secondary yolk sac and chorionic cavity - no connection with mom yet
Primary villi established
Connecting stalk attaches embryo to chorion
Primary chorionic villi are formed

Day 15-
Laterality established
•Cranial: oropharyngeal membrane
•Caudal: primitive node (2/3 to end) + primitive streak
Gastrulation begins with primitive streak

End of week: formation of primitive streak and establishment of Cranial-Caudal Axis

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What is happening in week 3?

Day 16 - secondary stem villi form (extraembryonic mesoderm invade)

Day 17- Neurulation Begins

Day 19 - myocardiogenesis begins

Day 20 -Gastrulation begins
Neurulation is complete
First somite appears (44 pairs total)
Heart tube begins to form through body folding

Day 21 - Tertiary villi form (connective tissue and blood vessels form), Lateral body folding begins
Hepatic cords form

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What is happening in week 4?

Neural Crest cells originate
Gastrulation is complete
Vertebrae form by scleretome

Heart pushed into chest by craniocadual folding

Esophagus begins to form and separates from lung bud

Stomach induced by Barx-1

Spleen arises from mesenchymal condensation of dorsal mesogastrium

Pronephros begins to form (completely degenerated by end of the week)

Mesonephros begins forming at end of the week

Forms primitive collection and filtration system (glomerulus + Bowman’s capsule + tubule = nephron)

Day 22- Heart tube begins to beat
Lateral body folding constricts yolk sac into the vitelline duct

Day 23- Heart begins to loop

Day 24 - Heart begins pumping blood

Day 27 - Septum primum begins to form

Day 28 - heart looping ios complete, heart septation begins, Gut tube is formed
L and R primary lung buds form (continue into 5th wk)

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What is happening in week 5?

Anus formed by rupture of the cloacal membrane

Gut tube is formed and attached by dorsal mesentery

Midgut enhanced by FGF9

PGC have migrated to the gonadal region (spermato- and oogenesis begin)

Day 33 - Septum secundum is formed

Day 35 - outflow tract septum of heart is formed, gut tube is attached to dorsalwall by mesentary

Lung buds branch into secondary buds (continue into 6th wk)

Metanephros starts to appear at the beginning of the week

Extrenal genitalia begin to differentiate

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What’s happening in week 6?

Cartilage templates formed by condensation of chondrocytes for endochonrdal ossification

Intestinal tube elongates (WNT5a, Pdx-1, Cdx-2)

Small and large intestines separated and primordium of cecum formed

Day 37 - Septum primum is completely formed, muscular ventricular septum is formed in heart

Day 42 - Atrioventricular septum is formed
Intestinal herniation begins (runs into 7th week)

Cloaca divided into rectum and urogenital sinus (continues into 7th week)

Neural crest cells migrate into foregut (continues into 7th week)

Lung buds continue branching to form tertiary lung buds (continues into 7th wk)

Primitive sex cords form

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What’s happening in week 7?

Foramen ovale is formed

Mitral and tricuspid atrioventricular valves are formed from atrioventricular cushions

Wolffian and Mullerian ducts differentiate

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What happens in week 8?

Day 56 - Coronary sinus is formed

Day 51 -cell death occurs in interdigital spaces to produce separation of digits

Day 56 - fingers and toes are present and limbs have undergone rotation

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What is happening in week 9?

Day 62- functional heart is complete

Intestinal loop begins to move back into body cavity

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What happens in week 12?

Vitelline duct degenerates (continues into 14th week)

Urine production begins

External genitalia is distinguishable

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When do the terminal bronchioles form?

week 16

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When do the first terminal sacs form in the lungs?

Week 28

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When do the terminal sacs begin to differentiate into mature aveoli?

week 36

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What roles does Luteinizing hormone (LH) play in development?

acts on Leydig cells to produce testosteron

promotes survival of the corpus luteum (preps endometrium for implantation)

helps follicle mature

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What roles does FSH play in development?

acts on sertoli cells to promote spermatogenesis

helps follicle mature

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List as many roles of FGF in development as you can.

High concentration in development of fore/midbrain

high for formation of hindbrain and spinal cord

FGF8 inhibits E-cadherin so cel can migrate in gastrulation

FGF2 and FGFR signal mesodermal cells in the heart

plays a role in specification of md-, hindguy, liver, billary, and pancreatic progenitor differentiation

expressed int he lung buds to stimulate outgrowth (select inhibition by TGF-beta1 creates branching)

FGF2 stimulates proliferation of uteric bud

FGF10 initiates limb outgrowth, FGF4 and FGF8 are expressed by AER to maintain progress zone, FGFs are closer to the AER (promotes autopod differentiation)

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List as many roles of BMP in development as you can.

low in formation of fore/midbrain activates WNT and acts w/ WNT on hypaxial region of myotomes upregulated in formation of heart specifies hindgut, high -> liver, low -> pancreas involved in lung bud outgrowth and development expressed by uteric bud and stimulate proliferation induces AER and is restricted to distal portion

List as many roles of WNT in development as you can.

high concentration in hindbrain/spinal cord activated by BMP in MSK development, acts with Shh on somites -> PAX3 to form dermatome and on epaxial region, works with B-catenin to help mesenchymal cells transition to osteoblasts (later inhibited by Osx) downregulated int he heart inhibited Hex, Sox-2, and Foxa-2 in esophagus, inhibited by BARX-1 in stomach, WNT-5a important in midgut and important in hindgut, elongaates intestinal tube involved in terminal bronchioles and respiratory bronchioles expressed by utereric buds to convert mesenchyme into epithelium that can form nephrons, upregulate PAX and WNT4 mesenchyme to help with tubule formation WNT4 to induce DAX1 for female development (ovaries) expressed dorsoventral

List as many roles of Shh in development as you can.

Expressed in notochord and floor plate, Induce MHP From bottom of notochord, acts on somite to form sclerotome (express PAX1), which contributes to vertebral formation Released from bottom of notochord with noggin to act on ventral somite to form sclerotome, acts with WNT on somites for dermatome and epaxial region involved in pancreatic progenitor cells promotes development of zeugopod (middle part of limb), and more in posterior part, ZPA and Shh posterior only and patterns limbs - get more digits if this is incorrect

List as many roles of Noggin in development as you can.

released from notochord and acts with Shh to create sclerotome (from ventral somite) inhibits BMP in neurulation (BMP prevents hinge points from forming)

List as many roles of PAX in development as you can.

PAX1 contributes to sclerotome formation (activated by Shh and Noggin) expressed by NC cells in gut induces differentiation into various types of endocrine pancreatic cells promotes tubule formation in the metanephric mesenchyme

List as many roles of MYOD and MYF5 in development as you can.

transcription factors expressed in the hypaxial and epiaxial region respectively

List as many roles of Retinoic Acid in development as you can.

effects expression of HOX genes in MSK development (high = anterior, low = posterior) specifies the hindgut induces expression of FGF10 in lung buds to promote outgrowth promotes differentation of stylopod in limb formation

List as many roles of VEGF in development as you can.

expressed by chondrocytes to promote endochondrial ossification they signal formation of vessels in the heart

List as many roles of Ihh in development as you can.

invovled in 1st stage of mesenchymal transition to osteoblasts

List as many roles of B-catenin in development as you can.

works with WNT to induce mesenchymal cell transition to osteoblasts

List as many roles of NKX in development as you can.

nkx2.5 master regulator of heart development important in ventricles expressing HAND1 and 2 (can result in ASDS) expressed in spleen primordium nkx2.1 involved in lung bud growth

List as many roles of NODAL in development as you can.

acts with LEFTY2 -> PITX2 (provides sidedness of heart)

List as many roles of lefty2 in development as you can.

acts with NODAL to express PITX2 and provide sidedness to heart

List as many roles of HAND1 and 2 in development as you can.

activated by NKX2.5 ``` 1 = left ventricles 2 = right ventricles ```

List as many roles of Barx-1 in development as you can.

develops stomach

List as many roles of Cdx-1,2 in development as you can.

involved in development of hindgut, intestines, pancreas, liver, cecum, cloaca, cdx-2 elongates intestinal tube

List as many roles of Pdx-1 in development as you can.

faciliates development of glandular system elongates intestinal tube expressed by pancreatic progenitors

List as many roles of Activin in development as you can.

involved in pancreatic development

List as many roles of TBX4/5 in development as you can.

5 results in heart hand syndromes, ASDs, and others expressed in mesenchymal tissue surrounding lung buds to induce FGF (stimulate outgrowth) influences limb outgrowth (5 = forelimb, 4 = hindlimb)

List as many roles of TGF-beta1 in development as you can.

involved in hepatoblasts with notch forming illary cells expressed in center of lung buds to inhibit FGF -> branching

List as many roles of WT-1 in development as you can.

prime metanephros for induction by ureteric bud and activate GDNF and HGF which stimulate the growth of the ureteric buds

List as many roles of DAX-1 in development as you can.

activated by WNT4 and contributes to ovary formation, inhibits SOX9

List as many roles of SOX9 in development as you can.

involved in liver bile ducts SOX9 is activated by SRY in males, inhibits WNT4, activates SF1 to form testes

What systems would be affected if FGF was knocked out?

``` notochord formation gastrulation MSK Heart Digestive Respiratory Urinary/Renal Genital Limb ```

What systems would be affected if BMP was knocked out?

``` notochord MSK heart digestive respiratory urinary/renal limb ```

What systems would be affected if WNT was knocked out?

``` MSK heart digestive respiratory Urinary/renal genital limbs ```

What systems would be affected if Shh was knocked out?

neurulation MSK digestive limb

What systems would be affected if Noggin was knocked out?

neurulation | MSK

What systems would be affected if PAX was knocked out?

MSK digestive urinary/renal

What systems would be affected if MYOD and MYF5 was knocked out?

muscle development

What systems would be affected if RA was knocked out?

MSK digestive respiratory limbs

What systems would be affected if VEGF was knocked out?

MSK (BONE DEVELOPMENT) | heart

What systems would be affected if NKX__ was knocked out?

heart digestive system (glandular) respiratory system

What systems would be affected if HAND1,2 was knocked out?

heart (ventricles)

What systems would be affected if Cdx-1,2 was knocked out?

digestive system

What systems would be affected if Pdx-1 was knocked out?

glandular system

What systems would be affected if TBX4/5 was knocked out?

respiratory | heart

What systems would be affected if TGF-beta1 was knocked out?

``` digestive system (billary) respiratory system (lung branching) ```

What systems would be affected if SOX9 was knocked out?

testes wouldn't develope

What systems would be affected if DAX1 was knocked out?

ovaries wouldn't form