1 - Neuroembryology Flashcards
what environmental factors can cuases neurodevelopment defects?
alcohol
tobacco
nutrional deficiencies
Outline the basic developmental stages in the first 12 weeks of pregnancy, during the weeks:
1. week 0
2. week 2
3. week 3
4. week 3-8
- implantation
- blastulation
- gastrulation
- organogenesis
Outline the process of implantation in 6 steps:
- Blastocyte enlarges as it obtains nutrients from glycogen rich fluid secreted from endometrium.
- On contact with endometrium - trophoblast cells in blastocyte divide rapidly increasing thickness of throphoblast layer.
- Cytotrophoblasts (closest to interior) differentiate into syncytiotrophoblasts – break down stratum functionalis by secreting hyaluronidase
- Produce hCG – binds to CL + sustains it.
- Decidual change
- Blastocyst is burrowed into stratum functionalis + endometrium closes
outline the 4 major outcomes in blastulation:
- Trophoblast differentiates into two layers – cytotrophoblasts and syncytiotrophoblasts
- Embryoblast forms two layers – hypoblast + epiblast
- Extraembryonic mesoderm – somatic layer + splanchnic layer
- Two cavities form – amniotic cavity + yolk sac
in what weeks does embryogenesis occur?
0-8
in what week does gastrulation occur?
week 3
what occurs in week 3 of fetal development?
gastrulation
outline the 3 basic steps of gastrulation:
- Primitive streak formed on base of amniotic cavity
- Epiblast cells migrate towards the streak and slip beneath it – invagination
- Leads to formation of 3 germ layers
what are the 3 germ layers formed during gastrulation called?
- ectoderm
- mesoderm
- endoderm
what does the ectoderm give rise to?
nervous system
during what weeks does organogenesis occur?
weeks 3-8
at what point in fetal development does the nervous system begin to form?
between 19-21 days AF
when does most nervous sytem development occur?
during embryogenesis
what are the 3 stages of nervous system development?
- induction of neural plate
- patterning of CNS
- neuronal differentiation/neurogenesis
the mesoderm develops into what?
somites –> skeletal and muscle tissue
the endoderm develops into what?
epithelium of organs
what process leads to the formation of the neural plate?
gastrulation
what forms directly beneath the primitive streak from mesoderm cells?
notochord
what is the notochord composed of?
mesoderm cells
what is the role of the notochord?
secretes growth factors which stimulates the differentiation of ectoderm into neuroectoderm
in what week of development does the notochord appear?
third week
describe the folding of the neural plate
3 steps
- median hinge point forms - notochord signalling
- lateral hinge points form - signalling from nearby mesoderm
- meet in midline to form neural tube
what structure forms as the neural folds fuse?
neural crest - then delaminates and migrates
what does the neural crest give rise to?
a diverse cell lineage incl. melanocytes, craniofacial cartilage and bone
when is neurulation achieved by?
end of the fourth week of development
in 4 steps, outline the induction of the neural plate to form the dorsoventral axis
- induction
- elevation
- convergence
- closure
in what region does neurulation first occur?
cervical region
what happens after neurulation occurs in the cervical region?
- neural tube zips up toward head and tail
- leaves anterior and posterior neuropores
when does the anterior neuropore close?
day 25
when does the posterior neuropore close?
day 28
what occurs if the anterior neuropore fails to close?
anencephaly - loss of telencephalon
usually results in death
what happens if the posterior neuropore fails to close?
spina bifida
what is the main goal of patterning of the nervous system?
helps cells acquire specific identities
what are morphogens?
secreted proteins that act in a dose dependent manner
what are the two main morphogens that act across the dorsoventral axis of the neural tube/
BMP - bone morphogenetic protein
SHH - sonic hedgehog
w
what morphogen is secreted in the dorsal “roof plate” of the nervous system?
BMP
what morphogen is secreted in the ventral “floor plate” of the nervous system/
SHH
what determines the identities of neurons along the DV axis?
combination of SHH and BMP gradients
a cell with motor neuron status has what relative levels of SHH and BMP?
high SHH
low BMP
list these transcription factors according to location in the dorsoventral axis:
* Olig2
* pax7
* pax6
* Nkx6.1
(from most dorsal to most ventral)
- Pax7
- Pax6
- olig2
- Nkx6.1
what is the antero-posterior axis also known as?
rostral-cordal axis
how is the nervous system patterned along the AP axis?
- posterior region secretes fibroblast growth factor
- somites (found centrally) secrete reinoic acid
- forms opposing gradients
- cells closer to RA secretion acuire spinal cord identity
what determines patterning in the anterior part of the CNS (the brain, not the spinal cord)?
combination of the morphogen signals from DV axis and diffusible molecules from AP axis
holoproscencephaly
failure of the proscencephalon (embryonic forebrain) to divide into two hemispheres
what causes holoprosencephaly?
mutation in SHH
morphogens are responsible for patterning the AP axis. what else is required for this?
homeotic genes
what is neurogenesis?
process through which nurones are formed in the developing embryo
neural progenitor cells are polarised. at which surface do they proliferate - apical or basal?
apical (nucleus moves back and forward from apical to basal surfaces)
in early development, how do progenitor cells divide?
symmetrically- equal inheritance of polarity complex proteins
during later stages of development, how do progenitor cells divide?
- asymmetically
- one daughter cell becomes a neuron
- other dauther cell becomes a progenitor cell and divides again
