Exam 3 Flashcards
receptor
A receptor is a protein molecule located on the surface of or within a cell that binds to specific signaling molecules, called ligands, and initiates a cellular response.
signaling molecule
A signaling molecule is a molecule that carries information from one cell to another, usually through binding to a specific receptor on the surface of the target cell.
signal reception
Signal reception refers to the process by which a cell detects and responds to extracellular signals or stimuli through the binding of signaling molecules to specific receptors on the cell surface or within the cell.
signal transduction
Signal transduction is the process by which extracellular signals or stimuli are transmitted into the cell, leading to a cellular response. It typically involves a series of biochemical reactions that relay the signal from the cell surface or receptor to the cell interior, often involving the activation of intracellular signaling pathways and the modulation of gene expression, protein activity, or cellular processes.
signal response (final response)
Signal response, or final response, refers to the ultimate cellular or physiological changes elicited by a signaling pathway in response to extracellular signals or stimuli.
signal deactivation
Signal deactivation refers to the process by which cellular signaling pathways are terminated or attenuated after the initial signaling stimulus has been received and the cellular response has been elicited.
kinase cascade
A kinase cascade is a series of sequential phosphorylation events in which one kinase phosphorylates and activates another kinase, leading to amplification and propagation of a signaling pathway.
dimer (dimerize)
A dimer is a complex formed by the association of two identical or similar molecules, called monomers. Dimerization refers to the process by which these monomers come together to form a dimer.
Describe the components and the general process of signaling – reception, transduction, final
response, deactivation.
Reception:
- Signal molecules (ligands) bind to receptor proteins
- Receptors can be on cell surface or inside the cell
- Binding causes conformational change in receptor
Transduction:
- Conformational change in receptor triggers signal transduction pathway
- Involves sequential activation/modification of relay molecules
- Relay molecules include kinases, phosphatases, GTPases, etc.
- Amplifies and propagates signal within the cell
Response:
- Activated relay molecules regulate activity of effector molecules
- Effectors include transcription factors, enzymes, ion channels
- Transcription factors modulate gene expression
- Enzymes catalyze biochemical reactions
- Ion channels control ion flow and membrane potential
- Integrated responses lead to cellular changes (metabolism, movement, division, etc.)
General Process:
- Extracellular signal → receptor binding → transduction pathway → effector activation → cellular response
Be able to recognize the general steps of signaling in a diagram or word problem
Reception:
- Ligand (signal molecule) binding to receptor protein
- Receptor shown on cell surface or inside cell
Transduction:
- Activation/modification of relay molecules (kinases, phosphatases, GTPases, etc.)
- Sequential steps showing propagation of signal
- Arrows indicating direction of signal flow
Response:
- Activation of effector molecules (transcription factors, enzymes, ion channels)
- Cellular processes/changes resulting from effector activation (gene expression, metabolism, movement, etc.)
General Flow:
- Diagram/description should show progression from:
1. Extracellular signal (ligand)
2. Receptor binding
3. Relay molecule activation (transduction pathway)
4. Effector molecule activation
5. Cellular response/change
The key is identifying the reception, transduction, and response components and tracing the directional flow from signal to cellular outcome.
Be able to interpret the consequence of a change/mutation in a signaling pathway.
- Identify the specific component affected (receptor, relay molecule, effector)
- Determine if the change leads to:
- Gain of function (increased/constitutive activity)
- Loss of function (decreased/blocked activity)
Potential consequences:
- Receptor mutation:
- Gain of function = constant signal, even without ligand
- Loss of function = inability to receive signal
- Relay molecule mutation:
- Gain of function = amplified/unregulated signal propagation
- Loss of function = blocked signal transmission
- Effector mutation:
- Gain of function = effector constantly active
- Loss of function = inability to activate effector
- Consider downstream effects on cellular processes regulated by that pathway
- Cell cycle, metabolism, differentiation, apoptosis, etc.
- Interpret in the context of the specific cell type/tissue
- Effects may differ based on the pathway’s role
The key is tracing the functional impact of the mutation through the pathway, and deducing the potential cellular consequences based on the pathway’s normal role.
totipotent
Totipotent refers to the ability of a single cell to give rise to all cell types in an organism, including both embryonic and extraembryonic tissues, as well as supporting structures such as the placenta.
pluripotent
Pluripotent refers to the ability of a cell to differentiate into cells derived from all three germ layers of the embryo: ectoderm, endoderm, and mesoderm.
multipotent
Multipotent refers to the ability of a cell to differentiate into a limited number of cell types within a specific lineage or tissue type. Unlike pluripotent cells, which can differentiate into cells from all three germ layers, multipotent cells are more restricted in their differentiation potential and can give rise to a limited range of cell types within a particular lineage or tissue.
asymmetric cell division
Asymmetric cell division is a process in which a parent cell divides unequally to produce two daughter cells with distinct fates or properties. One daughter cell typically retains the characteristics of the parent cell, while the other daughter cell undergoes differentiation to acquire a specialized function or fate. This process is crucial for generating cell diversity during development and tissue homeostasis.
self-renewal
Self-renewal refers to the ability of a cell to undergo division and produce daughter cells that are identical to the parent cell, thus maintaining the cell’s population and characteristics over time. It is a fundamental property of stem cells, allowing them to proliferate and replenish themselves while also giving rise to differentiated cell types.
apoptosis (programmed cell death)
Apoptosis, also known as programmed cell death, is a tightly regulated process of cellular suicide that occurs in multicellular organisms. It plays essential roles in development, tissue homeostasis, and the elimination of damaged or unwanted cells. Apoptosis is characterized by distinct morphological changes, including cell shrinkage, chromatin condensation, DNA fragmentation, and the formation of apoptotic bodies, which are then engulfed and digested by neighboring cells or phagocytes.
primary vs. secondary sex characteristic
Primary Sex Characteristics:
- Develop during embryogenesis
- Direct reproductive organs and gamete production
- Examples:
- In males: testes, penis, seminal vesicles, prostate gland
- In females: ovaries, uterus, vagina, oviducts
Secondary Sex Characteristics:
- Develop during puberty
- Not directly involved in reproduction
- Influence by sex hormones (testosterone, estrogen)
- Examples in males:
- Deepening voice, facial/body hair growth, muscle mass increase
- Examples in females:
- Breast development, widening of hips, fat distribution pattern
Key Differences:
- Primary characteristics are essential for reproductive functions
- Secondary characteristics are non-reproductive traits influenced by hormones
- Primary characteristics develop before birth
- Secondary characteristics emerge during puberty
Both are important for overall sexual development and maturation, but primary characteristics directly facilitate the reproductive process.
primordial germ cell (PGC)
A primordial germ cell (PGC) is a precursor cell that gives rise to gametes (sperm and egg cells) during embryonic development. PGCs are specified early in embryogenesis and migrate to the developing gonads, where they undergo further differentiation and eventually differentiate into mature sperm or eggs. They are essential for the transmission of genetic information from one generation to the next.
differentiation
Differentiation is the process by which cells become specialized in structure and function to perform specific roles within an organism. It involves changes in gene expression and cellular morphology that lead to the acquisition of distinct characteristics and functions. Differentiation allows cells to adopt specific fates and perform specialized functions, contributing to the development and maintenance of tissues and organs in multicellular organisms.
biological sex
Biological sex refers to the classification of individuals as male or female based on their reproductive anatomy and physiology. It is determined primarily by genetic factors, such as the presence of sex chromosomes (XX for females, XY for males), which influence the development of reproductive structures and secondary sexual characteristics. Biological sex also encompasses hormonal and physiological differences between males and females, including differences in reproductive function and hormone levels.
Differences in Sex Development (DSD)
Definition:
- Congenital conditions where development of chromosomal, gonadal, or anatomical sex is atypical
Types:
- Sex Chromosome DSD
- Atypical number of X/Y chromosomes (e.g. XXY, XYY, XO)
- 46,XY DSD
- Typical male chromosomes, but atypical genital development
- 46,XX DSD
- Typical female chromosomes, but virilization of genitalia
Causes:
- Genetic mutations affecting hormone production/receptors
- Enzyme deficiencies disrupting hormone synthesis
- Environmental influences affecting hormone exposure
Consequences:
- Ambiguous genitalia at birth
- Discordance between internal/external genital development
- Potential issues with fertility, gender identity, hormone imbalances
Management:
- Multidisciplinary team (genetics, endocrine, psychology, surgery)
- Treatment tailored to specifics of condition
- Hormone therapy, surgery, psychosocial support as needed
Key Points:
- Spectrum of conditions with atypical biological sex characteristics
- Caused by genetic, hormonal, or environmental factors
- Can impact genital development, fertility, gender identity
- Requires specialized multidisciplinary care
Mullerian duct
The Müllerian duct, also known as the paramesonephric duct, is a paired embryonic structure present in both male and female embryos. In females, the Müllerian duct develops into the fallopian tubes, uterus, cervix, and upper two-thirds of the vagina, contributing to the female reproductive tract. In males, anti-Müllerian hormone secreted by the testes causes regression of the Müllerian ducts, while the Wolffian ducts develop into the male reproductive tract.
Wolffian duct
The Wolffian duct, also known as the mesonephric duct, is a paired embryonic structure present in both male and female embryos. In males, the Wolffian duct gives rise to the epididymis, vas deferens, and seminal vesicles, contributing to the male reproductive tract. In females, the Wolffian duct regresses under the influence of anti-Müllerian hormone secreted by the ovaries, while the Müllerian duct develops into the female reproductive tract.
Barr body
A Barr body is an inactivated X chromosome in the cells of female mammals. It appears as a condensed, darkly staining structure within the nucleus of cells, representing one of the two X chromosomes in females that undergo random X chromosome inactivation during embryonic development. This process ensures dosage compensation between males (XY) and females (XX) by equalizing the expression of X-linked genes between the sexes.
SRY, WNT4, FOXL2
SRY (Sex-determining Region Y):
- Located on Y chromosome
- Master regulator gene for male sex determination
- Initiates male developmental pathway in bipotential gonad
- Triggers differentiation of Sertoli cells and testosterone production
WNT4 (Wingless-type MMTV integration site family, member 4):
- Key ovarian development gene
- Expressed in female bipotential gonad
- Promotes differentiation into ovarian structures
- Antagonizes male pathway, allows granulosa cell development
FOXL2 (Forkhead box L2):
- Transcription factor crucial for ovarian development/maintenance
- Mutations cause premature ovarian failure
- Regulates aromatase expression for estrogen production
- Represses testicular pathway genes in ovary
Key Points:
- SRY initiates male pathway, WNT4/FOXL2 promote female pathway
- Antagonistic roles in sex determination from bipotential gonad
- Disruptions can lead to disorders of sex development (DSD)
- Tightly regulated spatio-temporal expression required for proper development
Be able to describe and recognize the 5 shared developmental processes – cell division
(asymmetric and symmetric), signaling, differentiation, cell movement, and apoptosis.
Cell Division:
- Asymmetric: Daughter cells have different developmental fates
- Symmetric: Daughter cells are identical
Signaling:
- Cell-cell communication via signaling molecules/pathways
- Drives pattern formation, cell fate specification
Differentiation:
- Cells become specialized cell types
- Gene expression changes alter cell structure/function
Cell Movement:
- Cells migrate to specific locations
- Important for gastrulation, organogenesis
Apoptosis:
- Programmed cell death
- Removes unnecessary/defective cells
Recognizing in diagrams/problems:
- Asymmetric division: Distinct daughter cell fates
- Signaling: Ligands, receptors, signal transduction components
- Differentiation: Cells changing shape, markers of specialized types
- Movement: Cells relocating from one region to another
- Apoptosis: Controlled cell death/removal of cells
The key is identifying which of these fundamental processes is occurring based on the cellular behaviors and outcomes described.
Be able to describe biological sex development in XY and XX individuals, connecting where
the 5 shared developmental processes (#1) appear throughout the process.
XY Individuals:
- Embryonic gonadal ridge is bipotential (undifferentiated)
- SRY gene (Y chromosome) initiates male pathway
- Signaling for Sertoli cell differentiation
- Sertoli cells produce AMH, inhibiting female pathways
- Signaling, apoptosis of female precursor cells
- Leydig cells differentiate, produce testosterone
- Signaling for male duct differentiation
- Cell movement: Mesonephric ducts form male internal genitalia
- Cell movement: Genital tubercle elongates to form penis/urethra
XX Individuals:
- Embryonic gonadal ridge is bipotential
- No SRY, allows ovarian developmental pathway
- Signaling promotes follicle cell differentiation
- Follicle cells produce estrogen, inhibit male pathways
- Signaling, apoptosis of male precursor cells
- Asymmetric cell divisions in oogonia produce egg cells
- Cell movement: Paramesonephric ducts form female internals
- Cell movement, signaling in genital tubercle for labia formation
In both cases, signaling initiates sex-specific differentiation cascades, with subsequent cell division, movement and apoptosis events orchestrating the development of mature reproductive anatomy.
Describe and recognize hormone receptor signaling in sex hormone signaling during development AND recognize the basic processes of cell signaling
Hormone Receptor Signaling in Sex Development:
- Sex hormones (testosterone, estrogen, etc.) act as ligands
- Bind to nuclear or membrane-bound receptors
- Nuclear receptors: Direct transcriptional regulation
- Membrane receptors: Activate signaling cascades
Receptor Types:
- Nuclear (e.g. androgen receptor, estrogen receptor)
- Ligand-receptor complex acts as transcription factor
- Membrane (e.g. GPCR, RTK)
- Ligand binding triggers signaling cascade
Basic Cell Signaling Processes:
1. Reception: Hormone binds to receptor protein
2. Transduction:
- Relay molecules relay/amplify signal (kinases, etc.)
- Forms signaling cascade
3. Response:
- Activate effector proteins (transcription factors, enzymes)
- Modulate gene expression, cellular processes
Recognizing in Diagrams/Problems:
- Hormone as ligand binding receptor
- Nuclear receptor –> direct gene regulation
- Membrane receptor –> signaling cascade components
- Sequential activation of relay molecules
- Transcriptional changes or altered cellular processes
The key is identifying the hormone/receptor interaction that initiates the signaling, and tracing the flow through the transduction cascade to the ultimate cellular response.
Understand sex identity must be maintained through mutual inhibition of the other sex determination pathway.
Key Concepts:
- Bipotential gonad can develop into testis or ovary initially
- Mechanisms ensure one pathway is firmly established and upheld
- The pathways antagonize and repress each other
Mutual Inhibition in Males (XY):
- SRY initiates testis pathway
- Sertoli cells produce Anti-Müllerian Hormone (AMH)
- AMH induces apoptosis/regression of Müllerian ducts (female pathway)
- Prevents development of female reproductive structures
Mutual Inhibition in Females (XX):
- No SRY allows ovarian pathway progression
- Ovarian somatic cells produce Estrogen
- Estrogen antagonizes/suppresses testis pathway genes
- WNT4/RSPO1 block male pathway, maintain ovarian identity
Importance:
- Ensures complete differentiation into one gonadal fate
- Avoids ambiguous intersex characteristics
- Maintains appropriate hormone milieu for sex development
The key is the pathways repress antagonistic factors from the opposite pathway through opposing signals and apoptosis of precursor cell types. This reinforces the established identity.
Understand that sex is not determined by sex chromosomes in all species
Key Concepts:
- In mammals, X and Y chromosomes initiate male (XY) or female (XX) pathway
- However, many other sex determination systems exist across species
Examples of Non-Chromosomal Sex Determination:
Environmental Sex Determination:
- Temperature-dependent sex determination in many reptiles/fish
- High vs low temperatures during development dictate sex
Haplodiploidy:
- Found in insects like honeybees
- Males arise from unfertilized haploid eggs, females from fertilized diploid eggs
Complementary Sex Determiners:
- Certain genes/loci must be matched for an individual to be male or female
- Example: X:A ratio in some crustaceans and insects
Genomic Imprinting/Parent-of-Origin Effects:
- Parental origin of sex chromosomes determines sex in some fish and amphibians
Impact:
- Demonstrates the diversity of sex determination mechanisms evolved
- Chromosomes are just one of many possible sex-determining factors
- Underscores that no single universal mechanism exists across life
The key is recognizing that while sex chromosomes regulate sex in mammals, numerous other genetic, environmental, and epigenetic cues control this process in other organisms.
Be able to explain if a particular part of hormone signaling is disrupted what might occur – like the AR mutation
AR Mutation Effects:
- AR is the nuclear receptor that binds testosterone/DHT
- Required for male virilization and sex differentiation
Potential Consequences of AR Mutation:
- Androgen Insensitivity Syndrome (AIS)
- Partial or complete inability to respond to androgens
Partial AIS:
- Undervirilization in males
- Ambiguous genitalia, micropenis, hypospadias
- Gyneccomastia (breast development) at puberty
Complete AIS:
- XY genotype, but complete female phenotype
- Undescended testes
- Absence of male reproductive structures
- Tall stature, lack of pubic/axillary hair
Other Impacts:
- Impaired masculinization of brain (male gender identity issues)
- Reduced bone/muscle mass
- Potential subfertility/infertility
Key Points:
- Disruption of AR blocks ability to respond to androgens
- Prevents proper male sexual differentiation and development
- Severity depends on degree of receptor dysfunction
The effects stem from the critical role of AR signaling in facilitating androgen-directed male characteristics during development and puberty. Impairment leads to undervirilization or complete feminization.
Understand that DSDs demonstrate how complex sex development is and the consequence of disruption in regulation or response of the developmental process
Complexity of Sex Development:
- Tightly regulated processes and pathways govern sex determination and differentiation
- Involves interplay of genes, hormones, receptors, and signaling cascades
- Small perturbations can have significant downstream effects
DSDs Highlight This Complexity:
- DSDs arise from disruptions at multiple points in the developmental program
- Causes include genetic mutations, enzyme defects, hormone imbalances, etc.
- Result in atypical reproductive anatomy, hormone levels, puberty, fertility
Specific Examples:
- Androgen insensitivity syndrome (dysfunctional androgen receptor)
- Congenital adrenal hyperplasia (enzyme deficiency disrupts hormone levels)
- Ovotesticular DSD (ambiguous gonadal differentiation)
- Sex chromosome aneuploidies (atypical X/Y combinations)
Consequences:
- Undervirilization or feminization in males
- Virilization or masculinization in females
- Ambiguous genitalia, impaired fertility, developmental delays
- Psychosocial issues related to gender identity/body image
Key Takeaway:
- DSD conditions underscore how tightly regulated sex development is
- Demonstrate widespread effects when any part of the process is perturbed
- Highlight the complex biology governing biological sex determination
You do not need to memorize different DSD mutations. I would give you a developmental
pathway and ask you if something is mutated what would happen
Reception/Signal Initiation:
- SRY mutation → Failure to initiate male pathway
- WNT4/RSPO1 mutation → Failure to initiate female pathway
- Hormone deficiency → Lack of signal to drive differentiation
Transduction/Signaling Cascades:
- Effector mutation (β-catenin, SOX9, etc.) → Blockade of that pathway
- Kinase/relay mutation → Impaired signal propagation/amplification
Transcriptional Regulation:
- Nuclear receptor mutation (AR, ER) → Inability to respond to hormones
- Transcription factor mutation → Failure of cell fate/differentiation programs
Hormone Synthesis/Levels:
- Enzyme mutation (ex. CYP17) → Disrupted hormone production
- Over/underproduction → Abnormal hormone exposure
Cellular Processes:
- Cell migration defect → Abnormal anatomy/structure positioning
- Proliferation/Survival defect → Incorrect cell numbers/populations
- Apoptosis dysregulation → Persistence of precursor cell types
Key Considerations:
- Identify component’s normal role and position in pathways
- Determine if mutation causes loss or gain of function
- Trace potential downstream impacts on differentiation, organogenesis
- Consider timing of disruption (stages affected)
The key is logically deducing how altering that component’s activity could derail downstream processes required for proper sex phenotype development.
electrochemical gradient
An electrochemical gradient refers to the combined influence of both an electrical gradient and a concentration gradient across a cell membrane or within an organelle. It represents the difference in electrical charge (voltage) and concentration of ions (such as sodium, potassium, calcium, or chloride) between two sides of a membrane. The electrochemical gradient drives the movement of ions across the membrane, influencing various cellular processes such as ion transport, membrane potential, and the generation of action potentials.
chemical gradient
A chemical gradient, also known as a concentration gradient, refers to the gradual change in the concentration of a substance (e.g., ions, molecules) over a distance. It exists when there is a difference in the concentration of a substance between two regions, such as inside and outside of a cell or across a membrane. Substances tend to move down their concentration gradient from areas of higher concentration to areas of lower concentration, a process known as passive diffusion. The magnitude of the chemical gradient influences the rate and direction of diffusion and other transport processes across biological membranes.
electrical gradient
An electrical gradient refers to the difference in electrical charge (voltage) between two regions, such as across a cell membrane or within an organelle. It arises from the separation of charges across the membrane, with one side being more positively charged and the other side more negatively charged. The electrical gradient influences the movement of charged particles, such as ions, across the membrane, affecting membrane potential and electrical signaling in cells. Ions tend to move toward regions of opposite charge along the electrical gradient, a process known as electrostatic attraction or repulsion.
passive transport
Passive transport is a process by which substances move across a cell membrane or biological membrane without the input of energy from the cell. It occurs along the concentration gradient or electrical gradient and does not require the use of ATP. Passive transport mechanisms include diffusion, facilitated diffusion, and osmosis, which allow substances such as ions, gases, and small molecules to move freely across the membrane to achieve equilibrium.
facilitated diffusion
Facilitated diffusion is a type of passive transport in which substances move across a cell membrane with the help of transport proteins. Unlike simple diffusion, facilitated diffusion involves the movement of substances down their concentration gradient but requires specific membrane proteins, such as channels or carriers, to facilitate their passage across the membrane. Facilitated diffusion does not require energy input from the cell and is used for the transport of large, polar, or charged molecules that cannot freely diffuse across the membrane.
