Week 4 Flashcards
When does patterning occur in human development
- weeks 4-8 of embryonic development, human body form is established
Establishing anterior-posterior axis
Hox Genes
- homeobox DNA binding domain, regulates pattenrin along the AP axis
- vertebrates have 4 different complexes on 4 different chromosomes
- redudancy
- homeotic genes: genes that detemrine the fate of identity of body segments during development
- genes at 3’ end of the complex (numbered 1) are expressed earliest during development and their expression patternextend farther anterior
- 5’ end (higher number) expressed later and have more posterior expression patterns
homeotic genes
homeotic genes: genes that detemrine the fate of identity of body segments during development
colinearity
colineatrity: order of the genes on the chromosome reflects their temporal and/or spatial expression
HOX genes (5 rules)
- 3’ HOX genes expressed esarliest in development and have the most anterior boundaries of expression (temporal and spatial colinerarity)
- more hox genes are expressed in posterior regions (posterior prevalence)
- if several hox genes have overlapping expression patterns, the hox protein whose expression ends further posterior will detemrine the segmental phenotype (posterior dominance)
- Considerable redudanc in fxn exists in vertebrates
- demonstrate colinear expression along the primary AP axis of embry as well as along regional/organspecific embryonic aces (limbs, GI tract, female reproductive tract)
- temporal and spatial colinearity
- posterior prevalence
- posterior dominance
3’ HOX genes expressed esarliest in development and have the most anterior boundaries of expression (temporal and spatial colinerarity)
more hox genes are expressed in posterior regions (posterior prevalence)
if several hox genes have overlapping expression patterns, the hox protein whose expression ends further posterior will detemrine the segmental phenotype (posterior dominance)
HOX-D13 mutation phenotype
- expansion of a polyalanine strentch in HOX-D13: synpolydactyly
Establishment of doral-ventral axis and an anterior-posterior limb axis
- SONIC HEDGEHOG SIGNALING PATHWAY
- secreted from “organizing” or “patterning” centers during deelopemnt
- notochord:
- Shh diffuses dorsally: induces development of adjacent ectoderm into the neural tube, highest concentration of Shh induce diferentiaiton of the ventral floor plate and motor neurons in the ventral neural tube
- lower concentrations of Shh in doral neural tube associeated with development of sensory ganglia/neurons
- shh laterally from notochord affects development of adjacent somites (higher lateral concentration into sclerotome (rib precursor), low lateral concentartion develops into dermomytome (skin muscle wall)
-
zone of polarizing activity in the developing limb bud
- highest Shh on posterior limb side (5th digit)
- notochord:
Shh pathway overview + mutation consequences
Mutations in Shh…
Pathway inactivation: holoprosencephaly
Mutations in Ptc1…
Pathway activation (removing brakes on GLI): extra rib branches, asal cell nevus syndrome, verboid basal cell carcninoma syndrome (calcified hemispheres of brain, overseperated)
Mutations in GLI3…
Pathway activation: GLI3 is transcritpional repressor mostly, so remove repression and get actiation of extra digits: post-axial polydactyly type a or syndactyly
Week 1 developmental events
- ovulation
- fimbraiae of uterine tube fuide ovum to tube
- conception/fertilization->zygote formated->morula
- clinical timescale: begins first day of last normal menstraul period (2 weeks prior to ovulation) so clinical scale adds 2 weeks to biological conceptus
Week 2 developmental events
implantation and extraembryonic membrane formation
-
morula->hollow (blastocyst) which enters the uterine cavity
- blastocyst: outer shell, the trophblast, inner cell mass (will form embryo
-
implantation: blastocyst sinks into upper posterior uterine wall (endometrium or decidua)
- Ectopic preganacies are abdnomal implantation sties (cervix, tube, abdominal cavity)
- inner cell mass becomes hollow to form the amniotic cavity, now 2 cell layers: epiblast and hypoblast
-
Extraembryonic membrane formation
- trophoblast now has outer syncytiotrophoblast and inner cytotrophoblast
- primary amnion surrounding the amniotic cavity is continuous with the epiblast
- primary yolk sac becomes associated with hypoblast as a guiding Heuser’s membrane splits off from the cytotyophoblast, and hypoblast cells migrate over it
-
Extraembryonic mesoderm: coats the old blastocyst cavity to complete extraembryonic membrane formation
- chorion: syntrophoblast, cytotyophoblast, extra-ambryonic mesoderm
- amnion: ectoderm and extraembryonic mesodermal coat
- yolk sac: endoderm and extraembryonic mesoderm
Week 3 developmental events
gastrulation, intraembryonic mesoderm, creates a third germ layer, concucrrent with this is elongation of embryonic disc
- primitive knot forms a midline cord of mesoderm, notochord and primitive streak of ectoderm behind the primitive knot forms rest of intraembryonic mesoderm
- notochord: induces neural plate, remains as nucleus pulposis of intervertebral discs
- parazial columns: form segmental somites that form bone, muscle, dermis
- inermediate columns: urogenital systme
- lateral paltes: forms pleura, periotoneum, connective tissue of organs/body wall
- Neurolation (?)
