Module 1 Lecture 2: Axis Formation and Patterning Flashcards
what are the two important axes of an embryo
anterior-posterior and dorsal-ventral
what is the neural fold
the boundary between neural plate and outside ectoderm
what does the gastrula develop into
neurula
what do the neural folds do during neural tube closure
rise up, meet in the middle, and fuse
what does the notochord develop from
organizer
characteristics of notochord
- mesodermal
- critical role in D-V patterning
- transient in vertebrates; contributes to vertebral column (usually reabsorbed)
somites function
give rise to vertebrae and other musculo-skeletal elements
- either side of neural tube, mesodermal, segmental
neural crest function
makes PNS, melanocytes, face cartilage
- migrate away
- vertebrate specific, pluripotent
- born at epidermal-neural boundary
types of neural tube defects
- anencephaly
- spina bifida
what causes anencephaly
anterior neuropore fails to close
- brain absent or does not complete development
- fatal
what causes spina bifida
posterior closure fails
- survivable but leads to leg paralysis, loss of bowel and bladder control, hydrocephaly, and learning disabilities
role of folic acid in neurodevelopment
reduces risk of neural tube defects by 50-70%
three primary vesicles
forebrain, midbrain, and hindbrain
primary vesicles subdivided
- forebrain –> telencephalon, diencephalon
- midbrain –> mesncephalon
- hindbrain –> metencephalon, myelencephalon
what does the telencephalon subdivide into
olfactory lobes, hippocampus, cerebrum
what does the diencephalon subdivide into
optic residue, epithalamus, thalamus, hypothalamus
what does the mesencephalon subdivide into
midbrain
what does the metencephalon subdivide into
cerebellum, pons
what does the myelencephalon subdivide into
medulla
what triggers the development of the prospective forebrain from the ectoderm in the activation-transformation model
signal 1, “activation”
- neuralizes and specifies forebrain
- aka neural induction
what triggers the development of the midbrain in the activation-transformation model
signal 2, “transformation” (caudalizes)
- works in tension with activation & forebrain specification signals to induce more posterior structures
- signal coming from tail end
characteristics of signals coming from posterior end in activation-transformation model
soluble signaling molecules similar to BMP
what is the ultimate goal of the activation-transformation model
to change gene expression to specify neural fate
what does the shape of the activation-transformation effect depend on
interaction between caudalizing signal and dorsal mesoderm cells
what does Wnt overexpression cause
induction of head structures
what does Wnt inhibition cause
severe reduction of the head
how do vitamin A derivatives affect neurodevelopment
inhibits forebrain & midbrain development in a concentration-dependent manner
- consistent with a role in posterior neural tube specification
what does exposure to retinoic acid (RA) cause
craniofacial & brain malfunctions
first step of RA metabolism
make RA via retinaldehyde dehydrogenase (RALDH)
second step of RA metabolism
paracrine signaling
- broken by Cyp26
types of cell signaling
- autocrine: cell targets self
- gap junction signaling: cell targets a cell connected by gap junctions
- paracrine: cell targets a nearby cell
- endocrine: cell targets distant cell through bloodstream
third step of RA metabolism
response to RA: RA and retinoid X receptors heterodimerize & bind RA-response elements
- activate gene transcription
fourth step of RA metabolism
Cyp26 generates the “sink” and breaks RA
what is the next step after A-P patterning
regionalization
- organisms are not built step by step, but asynchronously in overlapping fashion
why is establishing segment identity (aka regionalization) important
critical to specification of cranial nerves, development of brain stem, inner ear, branchial arches, and the heart and large vessels
homeobox
a sequence of 180bp nucleotides which encodes a highly conserved 60aa DNA binding domain: homeodomain
what can a single homeotic protein do
-regulate (activate or repress) hundreds of different genes
what determines the target set of genes in a given cell
homeotic proteins mixing and matching with other transcription factors
co-linearity principle
Hox genes are organized in sequential clusters on chromosomes (eg 2 clusters on Chr3.)
how does the physical order of Hox genes on a chromosome map to their order of expression
physical order on the chromosome matches their order of expression in the AP axis of a developing animal
posterior dominance
activity of posterior Hox genes dominates over more anterior ones (if they are co-expressed)
homeosis
- or homeotic transformation
a variation in body plans in which “something has been changed to the likeness of something else”
master regulators
homeotic genes; they turn on and off expression of so many genes, enough to reprogram entire body parts
- every animal we know has Hox genes
what are Hox genes?
clustered, master regulators of gene expression that follow the co-linearity principle across phyla
what are rhombomeres
transient segments of the developing hindbrain
what drives regionalization of rhombomeres
retinoic acid-dependent Hox gene expression
- also follow colinearity principle
what makes RA
somites (RALDH)
what shapes the RA gradient
rhombomeres (Cyp26)
- shaped by where it is made and broken down
what interprets the RA gradient
Hox genes
result of vitamin A deficiency
no RA, Hox1b not expressed, hindbrain “anteriorized”
result of Cyp26 dysfunction
too much RA, expanded Hox1b, hindbrain “posteriorized”
what is a morphogen
a signaling molecule that 1. acts in a concentration dependent manner 2. on cells other than the source 3. to produce specific responses
characteristics of Wnt, FGF, and BMP as morphogens
their signaling gradient is shaped by where they are secreted from and where they are inhibited by antagonists
when does D-V closure occur
soon after neural tube closure
what are the 11 classes of neural progenitors set up by
expression domains of transcription factors
what do expression domains of transcription factors control
gene regulation and gene expression patterns
- set up the 11 classes of neural progenitors
when is Pax7 (dorsal determinants) most present
prior to neural tube closure
what genes are involved after neural tube closure
- Pax7 becomes more restricted
- Olig2 expands
- Nkx2.2 is established
what does removal of notochord cause
loss of floorplate and motor neurons in the spinal cord
what does transplanting the notochord to the side of the spinal cord do
gives you a second floor plate and a second set of motor neurons at the dorsal side of the spinal cord
what induces ventral fates in spinal cord
notochord, with a diffusable signal
what is hedgehog
a secreted protein
what causes development of Sonic hedgehog (Shh)
the notochord induces the floorplate to produce it
what happens when cells from intermediate spinal cord are cultured with Shh
expression of ventral fate markers
what does higher Shh concentration cause
more ventral fates
is Shh a morphogen?
yes
what is the DV patterning of the spinal cord established by
two opposing morphogen gradients:
1. shift from the ventral side (notochord and floorplate)
2. BMP and Wnt from the dorsal side (epidermis and roof plate)
