Embryology

Question 1

Define ovulation

Answer 1

• Ovulation is the release of a mature egg (oocyte) from a mature follicle at the ovarian surface, in response to a surge of luteinizing hormone (LH) from the pituitary. The fimbriae of the fallopian tube capture the egg and draw it into the tube. The oocyte at this stage is surrounded by the zona pellucida, a glycoprotein shell.

Question 2

What is the zona pellucida?

Answer 2

Zona pellucida is a glycoprotein shell which surrounds the oocyte.

Question 3

What cells are involved with the bilaminar disc?

Answer 3

Epiblasts, which face the amniotic sac, and the hypoblasts, which face the yolk sac

Question 4

Which cells give rise to the trilaminar disc?

Answer 4

Epiblasts cells

Question 5

What does the endoderm form?

Answer 5

linings of lung, liver, pancreas, urogenital, and GI tract

Question 6

What are the types of teratogens?

Answer 6

Maternal factors (diabetes, PKU)

Drugs

Infectious agents (TORCH)

Physical agents (radiation)

Question 7

What does TORCH stand for?

Answer 7

Toxoplasmosis

Syphilis

Rubella

Cytomegalovirus

Herpes

Question 8

What are some characteristics of teratogens?

Answer 8

Specific

Dose dependent

Time dependent (exposure at different stages may affect outcome differnetly) -> teratogen can not affect development of organ AFTER organ is made

Question 9

Describe the all or nothing effect?

Answer 9

During very early stages of pregnancy (0-2 wks) if the embryo is exposed to teratogens there is an all or none effect. This means that either the teratogen will cause a spontatneous abortion or it will do nothing at all.

Question 10

What effect does maternal diabetes mellitus have on the fetus?

Answer 10

3 fold increase in congenital malformations

risk due to glycemic control

specific malformations are… caudal regression, spine/lower extremity malformations, congenital heart disase, renal and CNS malformation

Question 11

What effect does maternal PKU have on fetus?

Answer 11

microcephaly, low IQ, heart defect

Question 12

What affects do cytotoxic drugs have on fetal development?

Answer 12

multiple malformations, most organ systems affected

Question 13

What effect does ethanol have on fetal development?

Answer 13

Growth retardation, IQ disability, CNS defect, fetal alcohol syndrome

Question 14

Retinoids (anti acne)

Answer 14

Severe malformations: craniofacial + CNS

Question 15

What effect does streptomycin have on fetal development?

Answer 15

Deafness

Question 16

What effect does valproic acid have on fetal development (anticonvulsant)?

Answer 16

Spina bifida, cardiac defects

Question 17

What effect does warfarin have on fetal development? (anticoagluant)

Answer 17

Nasal hypoplasia, bone stipling, short distal phalanges, small nails

Question 18

What are the kinds of anomolies?

Answer 18

Malformation (poor formation of tissue), deformation (unusual forces acting on normal tissue), disruption (breakdown of normal tissue)

Question 19

What does the paraxial mesoderm form into?

What about intermediate mesoderm?

What about the lateral plate mesoderm?

Answer 19

The paraxial mesoderm, immediately adjacent to the neural tube, will become segmental somites, and form muscle, bone, dermis, and connective tissue.

Intermediate mesoderm, just lateral on either side of the paraxial mesoderm, will develop into the kidneys and gonads.

Lateral plate mesoderm includes somatic mesoderm, which contributes to the body wall, and splanchnic mesoderm, which contributes to the gut wall, as well as pleura, peritoneum, and connective tissues.

Answer 20

Question 21

What does patterning mean? What is primary patterning? Secondary patterning?

Answer 21

Organization of embryonic cells inteo a 3-D body plan

Primary = establishing body plan

secondary = regional or organ axes

Question 22

What are the key milestones in fetal develpoment?

Answer 22

Question 23

What is spatial colinearity?

What is temporal colinearity?

Answer 23

spatial colinearity: order of genes in a cluster/complex maps an axis in develpoing embryo (i.e. 3’ genes expressed anteriorly, 5’ posteriorly)

Termporal colinearity = 3’ genes epressed earlier than 5’ genes

Question 24

What does posterior prevalence mean?

Answer 24

Question 25

What is the anterior posterior axes of the embryo?

Answer 25

Developed by HOX genes which are expressed spatially and temporally in different ways. HOX genes are organized in clusters in the genome. HOX genes closer to the 3’ end of the cluster tend to be expressed earlier and throughout the axes including anteriorly. HOX geenes closer to 5’ end tend to only be expressed posteriorly and later in development.

Question 26

If HOX A1 is located 3’ to HOX A3, what would you expect the phenotypes of knocking out each gene to be?

Answer 26

Because HOX A1 is 3’ to HOX A3, knocking out HOX A1 should cause a malformation more ANTERIOR to knocking out HOX A3.

Question 27

What happens when HOX B4 is knocked out?

Answer 27

For background, HOX B3 alone allows for the devleopment of the first cervical veterbrae (C1). Normally, HOXB4 + HOX B3 leads to the formation of the second veterbrae (C2). Therefore, without HOXB4, the second veterbrae actually develops into another first veterbrae (C1)

Question 28

What is posterior dominance mean?

Answer 28

The HOX gene whose expression pattern ends more posterior defines the phenotype of that segment. For example, HOX B4 + HOX B3. HOXB4 ends its expression pattern more posteriorly (near C2). Therefore, it causes the phenotype of C2. Without HOXB4, HOXB3 becomes dominant and C1 forms instead of C2

Question 29

What are HOX genes

Answer 29

Transcription factors which bind DNA and regulate other genes. Targets of HOX genes /mechanism for cell specificity unclear at this moment.

Question 30

What does schlerotome become?

Answer 30

Skeleton (ribs and vetebral bodies)

Question 31

How do Shh, Patched, and GLI interact?

Answer 31

Hedgehog (Hh) binds its receptor, which is called Patched (Ptc). In the absence of Hh, Ptc inhibits the downstream pathway. In the presence of Hh, Hh inhibits Ptc and the negative regulation of the pathway by Ptc is removed; the pathway becomes active. The transcription factors (Ci, GLI1, GLI2, and GLI3) are tightly regulated to determine whether they provide a signal that activates or inhibits downstream target genes. In the above diagram (+) indicates “activates the pathway” and (-) indicates “inhibits the pathway.”

Role of the Hedgehog signal transduction pathway in human disease

Mutations and abnormalities in the function of these genes have been associated with human disease (birth defects and cancer) that we may better understand by understanding the function of this pathway during development. Loss of function Shh mutations have been associated holoprosencephaly; an abnormality in the development of the ventral embryonic forebrain, causing abnormal septation of the cerebral hemispheres (abnormality in the patterning of the central nervous system). Patched mutations, which lead to constitutive pathway activation, cause basal cell nevus syndrome. This includes skull and rib abnormalities and a predisposition to cancer (abnormality in skeletal patterning and cell growth). Loss of function of GLI3 is associated by cephalopolysyndactyly or polydactyly (abnormality in patterning of the extremities +/- central nervous system).