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92 Cards in this Set
- Front
- Back
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Molecule in dorsal-ventral patterning of the limb
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Wnt7a
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Dorsal-ventral patterning of the limb requires signals from the:
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ectoderm
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Anterior-posterior pattering of the limb requires signals from the:
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zone of polarizing activity (ZPA)
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Molecule involved in anterior-posterior patterning:
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sonic hedgehog (SHH)
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Proximal distal patterning of the limb requires signals from the:
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apical ectodermal ridge (AER)
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Molecule involved in proximal-distal patterning of the limb:
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FGF
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An activating mutation in this receptor leads to achondroplasia, the most common form of dwarfism (the receptor serves to limit growth)
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FGFR3
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T/F: BMPs are sufficient to induce bone and cartilage formation
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true
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T/F: BMP's are necessary for normal skeletal development
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true
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Transcription factor necessary for bone formation in addition to BMP
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Cbfa
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Defect in this transcription factor causes cleidocranial dysplasis (defect in clavicle and skull, bones formed by intramembranous ossification)
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Cbfa
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Three types of kidneys in development
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pronephric, mesonephric, metanephric
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Hypospadias
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result from lack of fusion of urethral folds, retaining opening of urethral orifice on ventral side of penis
occurs in males |
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Androgen Insensitivity Syndrome
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also called testicular feminization
male with no androgen receptors female phenotype no internal genitalia have breasts because testosterone not able to destroy breast buds small testes with no functioning germ cells |
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Cryptochidism
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Undescended testes (bilateral or unilateral)
Sterility Risk of cancer |
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Dosage sensitive sex reversal (DSS)
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XY
SRY, so should be male but DUPLICATED DAX-1 on the X chromosome antagonizes SRY No testes |
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Congenital adrenal hyperplasia has a similar phenotype to what other sex developmental disorder?
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In utero androgen exposure
phenotype is female masculinization |
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What structures are derived from the mullerian ducts (paramesonephric ducts) in females?
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uterine and fallopian tubes
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Overall rate of detection of birth defects (%)
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3%
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What is the sequence and time of the 3 developmental stages
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pre-embryonic (0-2 weeks)
embryonic (3-8 weeks) fetal (8 weeks until birth/ 38 weeks) |
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What processes are in each of the 3 developmental stages
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pre-embryonic (fertilization to gastrulation)
embryonic (gastrulation to basic body plan eg. limb bud patterning, branchial arch and head development) fetal- maturation of organs |
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List the key events in human development in order
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gametogenesis, fertilization, cleavage, implantation, gastrulation, neurulation, neural crest formation, organ formation in each of the 3 germ layer, growth and maturation
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Explain how eye development is an example of how differentiation occurs sequentially
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The opic vesicle induces the overlying ectoderm to become the lens. The lens then induce additional differentiated cell fates from the optic vesicle, including ciliary body and iris. Lens also induce overlying ectoderm to become cornea
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What are correlation experiments
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right time right place; use in situ hybridization
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What are necessary experiments
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remove or decrease a single factor and measure effect; gene knockout
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What are sufficient experiments
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add of increase a single factor and measure effects; transgenic or knock-in mice
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What are correlation experiments
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right time right place; use in situ hybridization
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What are the 6 major signaling families
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Wnts, BMP, Hedgehog, steroids, FGF (fibroblast growth factor), 7 transmembrane/ G coupled
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What are necessary experiments
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remove or decrease a single factor and measure effect; gene knockout
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What are the four main transcription factor families
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Homeodomains, basic helix loop helix, zinc finger, high mobility group (HMG, eg SOX9, SRY)
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What are sufficient experiments
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add of increase a single factor and measure effects; transgenic or knock-in mice
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What conditions need to be met for data from humans to be classified as necessary?
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Clinical disease segreagates as single Mendelian gene
Mutation studies identify many mutations in different families Mutations in affected offspring of unaffected parent |
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What are the 6 major signaling families
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Wnts, BMP, Hedgehog, steroids, FGF (fibroblast growth factor), 7 transmembrane/ G coupled
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Give 3 examples of findings where correlation, necessary, and sufficient have been demonstrated
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Optic cup induces lens, H. pylori causes stomach ulcers, limb development through quail and chick transplantation experiments
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What are the four main transcription factor families
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Homeodomains, basic helix loop helix, zinc finger, high mobility group (HMG, eg SOX9, SRY)
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List 2 primary characteristics of transcription factors
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Must be able to recognize target sequence, i.e . through DNA binding regions
Must interact with the rest of the transcription machinery to alter the amount of RNA made from a target gene |
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What conditions need to be met for data from humans to be classified as necessary?
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Clinical disease segreagates as single Mendelian gene
Mutation studies identify many mutations in different families Mutations in affected offspring of unaffected parent |
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List the associated master regulator transcription factors for the following tissues
1. Muscle 2. Bone 3. Cartilage 4. Fat |
1. MYOD
2. Cbfa1 3. Sox 9 4. PPAR gamma |
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Give 3 examples of findings where correlation, necessary, and sufficient have been demonstrated
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Optic cup induces lens, H. pylori causes stomach ulcers, limb development through quail and chick transplantation experiments
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Hirschprung's disease: defect, symptoms
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Defect in cell signaling
Symptoms include aganglionic colon, megacolon, severe constipation and pigmentation defects in skin and eyes. This is because cells signal to neural crest cells to migrate, proliferate and differentiate into neural crest derivatives (which include neurons and melanocytes) |
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List 2 primary characteristics of transcription factors
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Must be able to recognize target sequence, i.e . through DNA binding regions
Must interact with the rest of the transcription machinery to alter the amount of RNA made from a target gene |
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List the associated master regulator transcription factors for the following tissues
1. Muscle 2. Bone 3. Cartilage 4. Fat |
1. MYOD
2. Cbfa1 3. Sox 9 4. PPAR gamma |
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Hirschprung's disease: defect, symptoms
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Defect in cell signaling
Symptoms include aganglionic colon, megacolon, severe constipation and pigmentation defects in skin and eyes. This is because cells signal to neural crest cells to migrate, proliferate and differentiate into neural crest derivatives (which include neurons and melanocytes) |
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When do primordial germ cells first appear in development
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2nd week post fertilization
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In what tissue does primordial germ cells first appear?
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epiblast
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What molecule activates PGCs in the epiblast i.e cause them to migrate and what experiments show this?
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BMP4
1. Correlation- BMP4 expressed in pgc in epiblast 2. Necessary- mutant mice with inactivating BMP4 mutation do not form PGC 3. Sufficient - add recombinant BMP4 and pgc will migrate in vitro |
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What is the major receptor involved in PGC migration and what is it's ligand
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cKIT tyrosine kinase and stem cell factor (ligand)
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What correlation experiments demonstrate the molecules involved in PGC migration
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Germ cells, neural crest cells (including pigment cells) and red blood cells (all the migrating type cells) share a common stem cell
survival factor, stem cell factor (ligand), and express cKit tyrosine kinase (transmembrane receptor) |
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What necessary experiments demonstrate the molecules involved in PGC migration
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Mutations in the stem cell factor (ligand) or the cKIT tyrosine kinase (receptor) affect fertility, pigmentation and blood cell development.
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What sufficient experiments demonstrate the molecules involved in PGC migration
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Add stem cell factor to PGC in vitro ->stimulate cell division and may
decrease cell death, promote chemotaxis. |
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What results from defects in germ cell migration
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extra-gonadal tumors (common neonatal tumor; typically cKIT positive)
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Retention of totipotency in the germ cell lineage correlates with the expression of homeodomain
transcription factors ____ and _____ |
Oct4 and Nanog
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Why is there an increased rate of sperm mutation with increased paternal age
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Increased number of mitoses (stem cell division occurs throughout life)
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What are some diseases that increase with paternal age
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Achondroplasia, Apert's syndrome, schizophrenia
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What is the sequence of sperm development?
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Spermatogonia, primary spermatocyte, meiosis 1 gives secondary spermatocyte, meiosis 2 gives haploid spermatids, spermatozoa (
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Why do the clone of sperm cells remain connected by cytoplasmic bridge
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Share diffusible X- chromosome gene
products |
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How long does spermatogenesis in humans take?
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62 days
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Define stem cell
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Cell with ability to self replicate and to enter differentiation pathway –
specialized cell types. A single cell has both sets of potentials (self renewal and differentiation pathway). |
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Where in the testes does spermatogenesis take place
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In the seminiferous tubules, in close association with the sertoli cells
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Define spermiogenesis
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Morphogenesis and differentiation of round haploid spermatids into highly polarized spermatozoa
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What are the key features of a mature human spermatozoa
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1. Haploid nucleus with specialized nuclear proteins called protamines (which replace histones in the spermatid)
2. A secretory organelle (acrosome) at the front of the sperm 3. Midpiece region with mitochondria around axoneme 4. Tail motor with Dynein ATPase axoneme |
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Male infertility: Kartagener syndrome
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Immotile cilia due to nonfunctional dynein arms (also have respiratory infections and situs inversus)
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Male Infertility: Klinefelter's men
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XXX
tall with long extremities, gynecomastia, presence of inactive X chromosome (Barr body). Individual Klinefelter men can now have fertility restored through assisted reproductive technologies (intra cytoplasmic sperm injection). normal intelligence. correlation between advanced paternal age and sex chromosome aneuploidies; older men have increased incidence of disomy for sex chromosomes. |
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What stage of development are eggs arrested in?
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prophase of meiosis I
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Compare and contrast the timing of meiosis in eggs vs sperm
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In egg, eggs arrested in prophase of meiosis I during fetal development, then after puberty will arrest cyclically at metaphase of meiosis II. Completion of meiosis occurs upon fertilization. Males keep stem cell spermatogonia throughout life and initiate meiosis at puberty.
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When do ova complete meiosis?
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After fertilization
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What findings show that c-kit is correlated, necessary and sufficient for oocyte development?
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Correlation: c-kit expressed on oocytes and granulosa cells
Necessary: If c-kit receptor bloked, follicles undergo atresia Sufficient: c-kit ligand permits cell locomotion |
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what cells synthesize zona pellucida glycoproteins?
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cumulus oophorus (granulosa) cells and oocytes
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List 10 steps in the process of fertilization
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chemotaxis of sperm to egg follicle
binding of sperm to egg zona pellucida acrosome reaction of sperm penetration of sperm through zona pellucida Fusion of sperm and egg plasma membranes Release of sperm-specific isoform of phospholipase c Transient peaks of intracellular free Ca++ inside zygote cytoplasm Egg microfilaments actively draw sperm into egg Onset of protein synthesis in zygote Egg cytoskeletal microtubules center the pronucleus of the sperm and egg First cleavage |
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5 roles of egg coat (extracellular matrix- zona pellucida) in fertilization
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1. sperm binging sites
2. induces acrosome reaction 3. species specificity 4. prevents polysoermy 5. protective coat around pre-embryi during pre-implantation development |
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Explain how intracellular free Ca++ is correlated, necessary and sufficient for fertilization
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Correlation: Ca++ increases at the right time and place (dyes reveal rise in Ca++ from point of sperm entry)
Necessary ( chelator of Ca++ prevents sperm from being effective) Sufficient (calcium ionophore can initiate early events) |
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Sequence of events in pre-implantation
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fertilization
cleavage onset of transcription by 8 cell stage formation of morula blastocyst comprised of inner cell mass and trophectoderm (trophoblast) two-layered bilaminar disc stage (epiblast and hypoblast) |
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What are some factors that can affect dizygotic twinning rates
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parity, maternal age, maternal diet
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What is an organizer
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transient embryonic region with the ability to induce major body elements, eg. primitive streak, AVE (anterior visceral endoderm), notochord
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How can you test for an organizer
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Transplant and look for host response
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What is the AVE (anterior visceral endoderm)
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Extra-embryonic tissue that is necessary and sufficient for induction of forebrain structures
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What is convergent extension and what genes are required for this?
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Process during gastrulation and neurulation where sheets of moving rearrange to extend along the body axis.
Planar Cell Polarity genes (PCP) |
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What day does neural tube closure begin?
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Day 22
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What day does implantation begin
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About 7-10 day, last about 1 week
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When is gastrulation
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By day 15
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When does the cranial neuropore close
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Day 24
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When does the caudal neuropore close
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Day 26
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Where on the embryo along AP axis does neural tube closure start
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Middle, proceeds outward in both directions in a zippering action
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What 2 main pathways are involved in neural tube defects?
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Planar cell polarity pathway and sonic hedgehog signaling pathway
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What signals control differentiation of the notochord along the DV axis?
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SHH from the notochord (induces floorplate, which then induces ventral motor neurons) and BMP from the overlying ectoderm (induces roof plate, which then induces sensory motor neurons)
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Give 3 examples of disorders resulting from defect in SHH signaling
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Gorlin's syndrome (Basal cell nervus syndrome) (too much SHH or too little Patched)
Holoprosencephaly (too little) Spina Bifida Polydactyly (too much) |
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What is the earliest functional organ in the embryo
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heart
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Malfunction of the heart in adults affect what 4 structures
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valves
muscle (cardiomyopathies) electrical conduction coronary arterial circulation |
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What are the key events of heart development sequentially?
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Formation of blood and blood vessel (~day 15)
Establishment of cardiogenic field Formation of heart tube Formation of heart loop Septation of heart tube Formation of heart valves Development of the conduction system |
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What 3 families of signaling molecules have major roles in establishing cardiac cell identitity?
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BMP
Wnt FGF |
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DiGeorge syndrome
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Deletion in chromosome 22q11, including Tbx1
Defect in neural crest Craniofacial, heart, thymus (immunological), parathyroid (hypocapcemia) defects |
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What is the most common type of congenital heart defects
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Vavular malformations, which mostly manifest in adults
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