[CLINICAL EMBRYO] Chapter 5: Third Week of Development: Trilaminar Germ Disc

Beginning of the 3rd week / gastrulation

Developmental stage that is highly sensitive to teratogenic insult

Organ-system cell populations

What can be damaged by teratogens during gastrulation because their future fates are already mapped?

Alcohol

High-dose teratogen specifically associated with anterior midline cell death in animal studies

Holoprosencephaly

Developmental defect caused by loss of anterior midline cells

Small forebrain

Brain abnormality associated with holoprosencephaly

Fusion of the lateral ventricles into a single ventricle

Ventricular abnormality that may occur in holoprosencephaly

Hypotelorism

Eye-position abnormality associated with holoprosencephaly

2 weeks after fertilization

Approximate time from fertilization when gastrulation begins

4 weeks from LMP

Approximate gestational age from the last menstrual period when gastrulation begins

Caudal dysgenesis (sirenomelia)

Condition caused by insufficient mesoderm formation in the caudalmost embryo

Caudal mesoderm

Mesoderm that is insufficient in caudal dysgenesis

Lower limbs, urogenital system, and lumbosacral vertebrae

Major structures affected because caudal mesoderm contributes to them

Hypoplasia and fusion of lower limbs

Lower-limb abnormalities associated with caudal dysgenesis

Lumbosacral vertebral abnormalities

Vertebral abnormality associated with caudal dysgenesis

Renal agenesis

Renal abnormality associated with caudal dysgenesis

Imperforate anus

Anal abnormality associated with caudal dysgenesis

Genital organ anomalies

Genital abnormality associated with caudal dysgenesis

Maternal diabetes

Maternal condition associated with caudal dysgenesis in humans

BRACHYURY (T), WNT, ENGRAILED

Genes whose abnormalities produce a similar phenotype in mice

Sacrococcygeal teratoma

Tumor caused by persistent remnants of the primitive streak in the sacrococcygeal region

Pluripotent cells

Type of cells that persist and form sacrococcygeal teratomas

They contain tissues from all 3 germ layers

Why do sacrococcygeal teratomas contain many different tissue types?

Sacrococcygeal teratoma

Most common tumor in newborns

Primordial germ cells that fail to migrate to the gonadal ridge

Other source of teratomas besides primitive streak remnants

Situs solitus

Normal positioning of the internal organs

Situs inversus

Mirror-image reversal of the positioning of all internal organs

Situs ambiguus / heterotaxy

Abnormal/disordered organ positioning caused by failure to properly establish the L-R axis

Heterotaxy

Condition in which organs are not completely reversed but show abnormal laterality

Polysplenia

Left-sided bilaterality associated with multiple spleens

Asplenia / hypoplastic spleen

Right-sided bilaterality associated with absent or underdeveloped spleen

Dextrocardia

Reversal of the heart's position to the right side

Kartagener syndrome

Condition associated with abnormal cilia, bronchiectasis, and chronic sinusitis

20%

Approximate percentage of complete situs inversus patients with bronchiectasis and chronic sinusitis

Heterotaxy

Laterality disorder associated with a high risk of multiple congenital abnormalities

Neural tube defects, cleft palate, anal atresia

Midline defects associated with heterotaxy

90%

Approximate percentage of heterotaxy patients with complex congenital heart defects

ZIC3

X-linked gene whose mutation can cause heterotaxy

X chromosome

Chromosome containing ZIC3

Neural tube defects, limb abnormalities, omphalocele, severe heart malformations

Other defects associated with X-linked heterotaxy

Serotonin (5-HT)

Neurotransmitter important for establishing left-right laterality

Situs inversus, heterotaxy, dextrocardia, heart defects

Laterality defects associated with disrupted 5-HT signaling

They may participate in L-R patterning

Why are cilia of the primitive node important?

SSRIs

Drug class mentioned as potentially associated with increased congenital defects when taken during pregnancy

Prozac, Paxil, Zoloft, Lexapro, Celexa

Examples of SSRIs mentioned