Embryo Development Patterning I Flashcards
During the _______ (weeks -) stages, a substance either damages most of the cells of the embryo, resulting in death, or damages only a few cells, allowing for embryo rescue.
During the PREDIFFERENTIATION (weeks 1-3) stages, a substance either damages most of the cells of the embryo, resulting in death, or damages only a few cells, allowing for embryo rescue.
Risks of birth defects from many teratogens are highest in ______ period (- weeks)
Risks of birth defects from many teratogens are highest in EMBRYONIC period (3-8 weeks)
Thalidomine:
If fetus is exposed at __-__ days, ____ are absent with early ___ ____ probably because ___ ___ ___ needed to support rapid growth ceases. Digits can be _____ or ____.
Thalidomide’s current uses: _____ and ____
Thalidomine:
If fetus is exposed at 24-36 days, LONG BONES are absent with early GROWTH STUNTING probably because THE BLOOD VESSEL GROWTH THAT’S needed to support rapid growth ceases. Digits can be NORMAL or FLIPPER-LIKE.
Thalidomide’s current uses: LEPROSY and MULTIPLE MYELOMA
TGF-beta and FGF pathways utilize _______ for signal transduction.
TGF-beta peptides bind as ____ to ____ receptors, leading to receptor _____. The activated receptor then _____ a protein called ____, which will ____ and enter the _____ to regulate _____.
_____ antagonize TGF-beta/____ action.
______ works by preventing TGF-like _____ from forming.
Antagonists of the antagonists such as ____ and ____ bind _____ monomer but produce a ____ that cannot ______ ____ receptors.
TGF-beta and FGF pathways utilize RTKs for signal transduction.
TGF-beta peptides bind as DIMERS to DIMERIZED receptors, leading to receptor PHOSPHORYLATION. The activated receptor then PHOSPHORYLATES a protein called SMAD, which will DIMERIZE and enter the NUCLEUS to regulate TRANSCRIPTION.
BMP-4 antagonize TGF-beta/NODAL action.
BMP-4 works by preventing TGF-like DIMERS from forming.
Antagonists of the antagonists such as NOGGIN and CHORDIN bind BMP-4 monomer but produce a DIMER that cannot ACTIVATE BMP-4 receptors.
FGF Signaling:
FGF exist at ____ but need to produce _____ receptors in order for activation. Some ___ bind ___ to present to _____.
FGFs are critical for _______ formation and development of ____, _____, and ____ systems.
Cell surface ______ presents FGF to ___ ___ receptors and helps stabilize active _____ receptor.
FGF Signaling:
FGF exist at MONOMERS but need to produce DIMER receptors in order for activation. Some PROTEOGLYCANS bind FGF to present to RECEPTOR.
FGFs are critical for EARLY AXIS formation and development of BONE, CARTILAGE and CIRCULATORY systems.
Cell surface HEPARAN SULFATE PG presents FGF to TYROSINE KINASE receptors and helps stabilize active DIMERIC receptor.
Two TFs required for two early embryonic lineages are initially ____ but expresison becomes gradually _____ via _______ even before _____ and _____ cells become completely sorted.
Two TFs required for two early embryonic lineages are initially CO-EXPRESSED but expresison becomes gradually RESTRICTED via RECIPROCAL INHIBITION even before TROPHECTODERM and ICM cells become completely sorted.
Mutation in _____ gene leads to prevention of _____ formation, prevention of ____, and prevention of ____ production.
____ is expressed in posterior region of embryo, where ____ begins and ____ will form.
____ is a TGF-beta-like peptide.
____ expression begins even earlier and introduces another important region of early embryo, the ____ ____ ____, which is required for differentiation of ___/____ structures
Induced _____ produces ____ that suppress ___ expression in most of embryo except for small region in ____ end (___).
There, at the ____ region, ___ expression increases to _____ level needed for ____ to form and ______ formation to begin.
Mutation in NODAL gene leads to prevention of PRIMITIVE STREAK formation, prevention of GASTRULATION, and prevention of MESODERM production.
NODAL is expressed in posterior region of embryo, where GASTRULATION begins and MESODERM will form.
NODAL is a TGF-beta-like peptide.
NODAL expression begins even earlier and introduces another important region of early embryo, the ANTERIOR VISCERAL ENDODERM, which is required for differentiation of ANTERIOR/HEAD structures
Induced AVE produces INHIBITOR that suppress NODAL expression in most of embryo except for small region in POSTERIOR end (NODE).
There, at the NODE region, NODAL expression increases to THRESHOLD level needed for MESODERM to form and PRIMITIVE STREAK formation to begin.
____ is highly expressed in hatched area. ____ suppresses mesoderm and nervous system formation and promotes _____.
BMP4 is highly expressed in hatched area. BMP4 suppresses mesoderm and nervous system formation and promotes EPIDERMIS.
Things that BMP-4 Suppresses
Things that Suppress BMP-4 (how?)
Things that BMP-4 Suppresses
- nodal
- mesoderm formation
- differentiation of dorsal mesodem (notochord and somites)
- nervous system production from ectoderm
Things that Suppress BMP-4
- noggin
- chordin
- they dimerize with BMP-4 monomer and prevents it’s association with receptors. This allows nodal expression to EXPAND and subsequent formation of dorsal mesoderm and neural induction.
Goosecoid is expressed in the ____. It’s a ___ that allows ____ structures to be induced by ____ moving in an ___ direction. Too much goosecoid can lead to _____.
Goosecoid is expressed in the NODE. It’s a TF that allows ANTERIOR structures to be induced by MESODERM moving in an ANTERIOR direction. Too much goosecoid can lead to AN EXTRA HEAD.
Brachyury is a _____ gene what affects ____ formation. It’s expressed in the _____. If it’s KOed, it produces a _____ phenotype.
Brachyury is a T-BOX gene what affects MESODERM formation. It’s expressed in the POSTERIOR. If it’s KOed, it produces a TAIL-LESS phenotype.
If there is not enough chordin, noggin, or brachury expression, ________ ______
If there is not enough chordin, noggin, or brachury expression, POSTERIOR MESODERM NEVER FORMS
FGF is also expressed in ___ ____ ____ giving rise to mesoderm. It induces a second region of ____ expression, which ultimately leads to ___-___ ____ axis. ____ is only expressed on one side of the embryo. FGF is needed for ______ development.
FGF in _______ promotes continued _____ and _____ expression, which in turn continue to inhibit _____ over a broader range of the embryo. The inhibition of _____ in the dorsal region promotes dorsal ____ formation as well as ____ tissue development from ectoderm.
FGF is also expressed in PRIMITIVE STREAK CELLS giving rise to mesoderm. It induces a second region of NODAL expression, which ultimately leads to LEFT-RIGHT SIDEDNESS axis. NODAL is only expressed on one side of the embryo. FGF is needed for CAUDAL development.
FGF in MESODERM promotes continued CHORDIN and NOGGIN expression, which in turn continue to inhibit BMP-4 over a broader range of the embryo. The inhibition of BMP-4 in the dorsal region promotes dorsal MESODERM formation as well as NEURAL tissue development from ectoderm.
Role of Retinoic Acic (RA) during development:
Endogenous RA is produced and normally active in only restricted areas of embryo where there are ____ receptors.
In absence of RA, reduced ____ structures and some transformation of ____ to ____ structures.
RA is expressed ______. It’s synthetic enzyme is expressed in this region at high levels. As RA is made from ____—>____, _____ is turned off.
As mesoderm is invaginating from caudal part, ____ are forming _____ to _____. These ____ give rise to _____ and ____.
Role of Retinoic Acic (RA) during development:
Endogenous RA is produced and normally active in only restricted areas of embryo where there are RA receptors.
In absence of RA, reduced POSTERIOR structures and some transformation of POSTERIOR to ANTERIOR structures.
RA is expressed ROSTRALLY. It’s synthetic enzyme is expressed in this region at high levels. As RA is made from ROSTRAL—>CAUDAL, FGF is turned off.
As mesoderm is invaginating from caudal part, SOMITES are forming ROSTRAL to CAUDAL. These SOMITES give rise to CARTILAGE and MUSCLE.
RA has reciprocal inhibitory interactions with ___.
-If too much RA, _____ turns off prematurely which will result in deficits in _____ structures.
RA has reciprocal inhibitory interactions with FGF.
-If too much RA, FGF turns off prematurely which will result in deficits in POSTERIOR structures.
