Quiz 6 Developmental Biology

Define a teratogen and list its three primary environmental classifications.

Any environmental factor that permanently disrupts embryonic development, causing structural or funtional defects.
Classifications: Physical (e.g., hyperthermia, loud noise), Chemical (e.g., caffeine alcohol), and Biological (e.g., viruses, bacteria)

Key Principles of Teratogens

Susceptibility depends on the embryonic stage during exposure (critical periods), genotype of the embryo/mohter, and dose/duration of the agent

Examples of Teratogens (Caffeine)

Chemical: Causes neural tube defects, failed neural tube closure. Decreased neuron proliferation, axon length, and disrupted D-V migratory paths of cranial neural crest cells. Cross-section shows failure of neural tube closure compared to control.

Examples of Teratogens (Loud Noise)

Physical: High db low hz most dangerous, triggers maternal neuroendocrine stress hormones like cortisol and catecholamines, vasoconstriction of uterine arteries, less oxygen flow, and cortisol can lead to low birth weight by limiting cell divison.

Germline Stem Cells (GSCs) vs. Somatic Cells

• GSCs (Primary/Primordial Germ Cells): Pluripotent (or arguably totipotent) cells whose daughters differentiate strictly into gametes (egg and sperm) to pass genetic info

• Somatic Stem Cells: Multi- or Unipotent cells whose daughters yield somatic cells to form structural tissues of the adult body

Other Names for GSCs

Primary germ cells and primordial germ cells (PGCs)

Explain the Autnomous/Germ Plasm mode of specification and describe the general roles of its maternally deposited regulators.

Maternally loaded mRNAs/proteins autonomously restrict cell fate to the germline early in cleavage, protecting them from somatic fate by regulating translation and inhibiting somatic transcription

Contrast how germ cells are specified early in development vs. organisms that convert cells throughout life

Some organisms set aside germ cells early in development via maternal germ plasm (e.g., Drosophila, Xenopus, C. elegans). Others can convert somatic cells to germ cells throughout life (e.g., certain flatworms)

How do the proteins inside P-granules specify the germline in C. elegans?

P-granules localize specifically to the P4 blastomere. They contain translation regulators (Vasa, Nanos, Piwi) and transcription inhibitors (PIE-1) that actively repress somatic genes to promote germ fate

What is the germ plasm called in Drosophila, what are its structural granules named, and what do the presumptive germ cells become?

The germ plasm is called pole plasm. It contains polar granules filled with translational regulators (Vasa, Nanos, Piwi). The presumptive germ cells are called pole cells

Describe the localization and behavior of germ plasm in Frogs (Xenopus laevis).

Germ plasm contains germinal granules (with Nanos, Vasa, Piwi) attached to the yolk. Following cortical rotation, they are released, fuse together at the Balbiani body, and migrate to the vegetal pole.

How are mammalian (mouse) germ cells specified compared to lower vertebrates/invertebrates?

Mammals have no germ plasm. Instead, PGCs are induced from the posterior epiblast by BMP signals traveling from the extra-embryonic ectoderm, prompting them to express Blimp1.

Embryonically, what tissue layer does the mammalian gonad arise from, and what is its specific anatomical zone?

Intermediate mesoderm along the genital ridge (also known as the urogenital ridge, as it gives rise to both the kidney and the gonads).

Describe the pathway Primordial Germ Cells (PGCs) use to reach the indifferent gonad in mammals.

PGCs multiply during migration, moving from the posterior epiblast/yolk sac wall through the hindgut and across the dorsal mesentary into the genital ridge

What guided tracking pathway controls PGC migration from the hindgut to the gonads?

Chemotaxis directed by the chemokine SDF1 (secreted by the genital ridge) binding to the CXCR4 receptor on migrating PGCs

Predict the developmental phenotypes of knocking down vs. overexpressing SDF1 or CXCR4

Knockdown: PGCs fail to reach the genital ridge, causing ectopic germ cells and sterility
Overexpression: PGCs are misrouted to abnormal, ectopic locations where the signal is elevated

Define a bipotential gonad

An early embryonic gonad derived from the genital ridge (or urogenital ridge) that is morphologically identical in XX and XY embryos, possessing the capacity to differentiate into either a testis or an ovary

Identify the male and female fates of the two core somatic lineages surrouding the PGCs: Supporting Cells and Interstitial Cells

• Supporting Cells: Sertoli cells surroud germ cells in the testis. Granulosa cells surround germ cells in the ovary

• Interstitial Cells: Leydig cells populate the testis spaces. Theca cells work alongside granulosa cells to build follicles in the ovary

Outline the genetic signaling loop that drives male vs. female primary sex determination in mammals

• Males (XY): The Y-linked SRY gene activates Sox9. Sox9 drives Fgf9 expression, forming a positive feedback loop that structuralizes the testis and actively represses Wnt4

• Female (XX): In the absence of SRY, Wnt4 (along with Rspo1) remains active, driving B-catenin to repress Sox9 and direct ovarian differentiation

Predict the gonadal phenotypes of: 1) An XY SRY or Sox9 knockout and 2) An XX Sox9 or Fgf9 overexpressor.

• Sex reversal to female (develops ovaries due to unhibibited Wnt4)

• Sex reversal to male (develops testes despite lacking a Y chromosome)

Differentiate between Primary and Secondary sex determination in mammals

• Primary: The determination of the gonadal phenotype (testis vs. ovary), strictly dictated by chromosomes/genes (Y chromosome dictates male sex regardless of X count).

• Secondary: The determination of the extragonadal physical traits (duct systems, genitalia), directed by hormones produced by the differentiated gonads

Explain how secondary sex determination shapes the internal duct and external genitalia options in mammalian females

Ovaries produce estrogen, enabling the Müllerian duct to form female internal genitalia (oviduct, uterus, cervix, upper vagina). The urogenital sinus/genital tubercle forms Skene’s glands, labia majora, and the clitoris

Explain how secondary sex determination shapes the internal duct and external genitalia options in mammalian males

Sertoli cells secrete Anti-Müllerian Hormone (AMH) to cause Müllerian duct regression. Leydig cells produce Testosterone to develop the Wolffian duct into male internal genitalia (epididymis, vas deferns, seminal vesicle). Testosterone converts to DHT to form the penis, prostate, and scrotum

Compare the heterogametic setups of XX/XY, ZZ/ZW, and XX/XO chromosomal systems.

• XX/XY: Male heterogamety (XY male, XX female); Y contains a dominant male-determining factor (SRY); mammals, Drosophila

• ZZ/ZW: Female heterogamety (ZZ male, ZW female); common in birds

• XX/XO: Male possesses only a single X chromosome (XO) and is haploid for that set, while females are XX (diploid); common in many insects

Detail the specific protective functions of the three conserved germ-plasm elements: Vasa, Nanos, and Piwi

• Vasa: An RNA helicase that activates the translation of germ-line specific mRNAs

• Nanos: A translational repressor that blocks somatic differentiation and prevents premature mitosis

• Piwi: An RNA-binding protein that epigentically silences transposable elements to protect genome integrity

Detail the inductive signaling cascade that specifies mammalian (mouse) PGCs instead of using a germ plasm

Cells in the posterior epiblast are primed by Wnt signaling during grastrulation, then receive BMP signals from the extra-embryonic ectoderm. This induces the strong expression of Blimp1, a master transcriptional repressor that shuts down the somatic program to establish germline fate.

Why must PGCs physically enter the somatic environment of the genital ridge to perform gametogenesis?

Reaching the specific somatic niche provides crucial signaling cues that prompt germ cells to halt normal mitosis and undergo mitotic arrest (males) or enter meiosis (females)

What specific tissue embryonic layer gives rise to the gonads and kidneys?

Intermediate mesoderm (On a 48h cross-section, locate it sandwiched directly between the paraxial somite blocks and the lateral plate mesoderm wings)

Map the anatomical derivatives of the bipotential duct structures (Müllerian vs. Wolffian) and external components for both sexes

• Female: Müllerian duct → Oviduct, uterus, cervix, upper vagina. Genital tubercle/Urogenital sinus → Clitoris, labia majora, Skene’s glands

• Male: Wolffian duct → Epididymis, vas deferns, seminal vesicle. Genital tubercle/Urogenital sinus → Penis, scrotum, prostate

Predict the internal duct phenotypes (Wolffian vs. Müllerian) for the following signal alteration: XY embryo with an SRY knockout

No testes form, meaning no AMH or Testosterone is produced. Müllerian ducts develop (uterus, oviducts) and Wolffian ducts degenerate (Phenotype: Female ducts)

Predict the internal duct phenotypes (Wolffian vs. Müllerian) for the following signal alteration: XY embryo with a Testosterone receptor knockout

Testes form and Sertoli cells secrete AMH, causing Müllerian ducts to degenerate. However, because testosterone cannot be sensed, Wolffian ducts also degenerate. (Phenotype: Neither duct system develops)

Predict the internal duct phenotypes (Wolffian vs. Müllerian) for the following signal alteration: XX embryo with a Wnt4 knockout

The default female pathway is disrupted, failing to properly repress male factors. Sox9 may become active, leading to partial sex reversal where Wolffian ducts persist/develop and Müllerian ducts are compromised. (Phenotype: Masculinized/Male ducts)

Predict the internal duct phenotypes (Wolffian vs. Müllerian) for the following signal alteration: XX embryo with a Sox9 overexpression

Excess Sox9 overrides the female Wnt4 signal, driving testis cord development. Ectopic Sertoli cells secrete AMH, causing Müllerian ducts to degenerate, while Leydig cells produce testosterone to develop Wolffian ducts. (Phenotype: Male ducts)

Differentiate between Chromosomal (GSD) and Environmental (ESD) sex determination

• GSD: Sex is locked at fertilization by the inherited chromosomal combination

• ESD: Sex is decided post-fertilization by external factors (e.g., Temperature-Dependent Sex Determination in reptiles where temperature changes aromatase enzyme activity).