Chapter 6: Establishment of the Basic Embryonic Body Plan Flashcards
neural plate
thickened cells visible on the dorsal surface of the early embryo; neural plate goes from producing N-CAM and E-cadherin preinduction to N-CAM and N-cadherin in the neural plate
first stage of neurulation
convergent extension
shaping of the neural plate so that it becomes narrower and longer; ectodermal cells forming the neural plate migrate toward the midline and also become longer along the posterior axis and narrower laterally
second stage of neurulation
neural groove and third stage of neurulation
third stage of neurulation
lateral folding of the neural plate that results in the elevation of each side of the neural plate along a midline neural groove
median hinge point
ventral midline of the neural plate that acts like an anchoring point around which the two sides become elevate at a sharp angle from the horizontal;
bending can be accounted for by notochord-induced changes in the shape of neuroepithelial cells of the neural plate (narrower at apex, wider at base)
basal position of nuclei and lateral expansion of cell in that area plus purse string-like contraction of ring of actin-containing microfilaments in the apical cytoplasm
lateral hinge point
[see Fig. 6-2, pg. 94]
forms as a result of apical constriction of cells in a localized area
fourth stage of neurulation
apposition of the two most lateral apical surfaces of the neural folds, their fusion (mediated by cell surface glycoconjugates), and the separation of the completed segment of neural tube from the overlying ectodermal sheet
neural crest cells begin to separate from neural tube
over the next days, closure of the neural tube extends caudally in a zipper like fashion, but cranially there are commonly two additional discontinuous sties of closure
anterior and posterior neuropores
unclosed cephalic and caudal parts of the neural tube;
ultimately close off so that the entire future CNS resembles an irregular cylinder sealed at both ends
secondary neurulation
occurs in mammals that have tails
segmentation of the neural tube vs. segmentation of somites
segmentation by subdivision of an existing structure (neural tube)
segmentation by adding terminal segments (somites)
three-part brain and its structures
prosencephalon (forebrain) –> telencephalon and diencephalon
mesencephalon (midbrain)
rhombencephalon (hindbrain) —> metencephalon and myelencephalon
neuromeres
neuromeres: certain regions of the brain are subdivided into transiently visible series of regular segments
rhombencephalon divided into rhombomeres and prosencephalon into prosomeres
rhombomeres
arranged as odd and even pairs; act like isolated compartments;
cells from adjacent rhombomeres do not intermingle across boundaries between even and odd segments
provide the basis for the fundamental organization of the hindbrain
segmentation of the neural tube
subdivided into forebrain/midbrain and hindbrain/spinal cord segments by inductions from notochord and head organizing regions and Wnt-8 gradient
forebrain/midbrain segment expresses Otx-2 (orthodenticle homologue 2)
hindbrain/spinal cord expresses Gbx-2 (gastrulation brain homeobox 2) ===sharply define midbrain-hindbrain border
isthmic organizer
midbrain-hindbrain border and powerful local signaling center
Wnt-1 is synthesized in the neural ectoderm anterior
FGF-8 is formed posterior to isthmic organizer
Pax-2 and Pax-5 and engrailed (En-1 and En-2) expressed on both sides of the isthmic organizer as gradients that are crucial in organizing the development of the midbrain and cerebellum
anterior neural ridge
signaling center located at the anterior pole of the brain; site of shh and FGF-8 signaling activity
important in formation of telencephalon, parts of diencephalon, olfactory area and pituitary gland
zona limitans
shh-secreting group of cells that organize the border between the future dorsal and ventral thalamus
rhombomere segmentation and genes involved
[see Fig. 6-4, pg. 96]
Lecture Notes Diagram
seven rhombomeres; segmentation genes are involved in setting up the basic pattern of segmentation that leads to rhombomere formation
Krox-20: zinc-finger TF expressed in and guides formation of r3 and r5
Kreisler and Hoxa-1 involved in formation of r5
decreasing gradient of retinoic acid produced by anterior somites plays important role in formation of posterior rhombomeres r4-r7
Gbx-2 regulates specification of r1 to r3
retinoic acid gradient stimulates the expression of Hoxa-1 and Hoxb-1 –initiates the expression of the various Hox paralogues in a highly specific sequence along the hindbrain and spinal cord
orderly expression of Hox gene paralogues extends anteriorly through r2; Hox proteins are not found in r1 because of antagonistic action of FGF-2 which is produced in response to signals from the isthmic organizer at the anterior end of r1
sprouty-2 acts as an antagonist of FGF-8 and this protein, in addition to Hoxa-2 in r2, confines FGF-8 to mostly r1 and contains the primordium of the cerebellum to the anterior part of r1
ephrins
ephrins and their receptors determine the behavioral properties of cells in the rhombomeres
ephrins are expressed in even numbered rhombomeres (2, 4, and 6) and ephrin receptors are expressed in odd numbered rhombomeres (3 and 5)
segmentation of spinal cord
segmentation of the spinal cord is to a great extent imposed by signals emanating from the paraxial mesoderm rather than from molecular signals intrinsic to the neural tube
somites forming, caudal-most part of the newly induced neural plate possess properties of a stem cell zone
FGF-8 causes these cells to proliferate without undergoing differentiation
retinoic acid (produced by newly formed somites) causes cells to differentiate into neurons
elongation of the tail bud region comes to a close when the caudal extent of presomitic mesoderm is reduced, thus allowing the retinoic acid produced in the area to diffuse farther posteriorly and inhibit the action of FGF-8
neural crest
leaves the dorsal part of the neural tube and begins to spread throughout the body of the embryo
produces a wide array of structures (“4th germ layer”)
ectodermal placodes
thickenings that appear lateral to the neural tube and neural crest
arise from preplacodal domain around the anterior neural plate that is established during gastrulation and early neurulation periods
cells from placodes and neural crest interact to form sensory ganglia of cranial nerves
paraxial mesoderm (segmental plate)
lateral to the neural plate; homogenous strip of closely packed mesenchymal cells
becomes organized into somites
somitomeres found in paraxial mesoderm;
somites
brick-shaped masses of paraxial mesoderm; form behind the seventh pair of somitomeres after almost 20 pairs of somitomeres have been formed and the primitive node has regressed quite far caudally
first seven somitomeres
do not undergo further separation or segmentation; cells from these are called cranial mesoderm and will form most of the skeletal musculature of the head
have quite different cellular and molecular properties from those derived from somites of the trunk
somitogenesis
somite formation;; first step is segmentation of the paraxial mesoderm
occurs by sequential addition of new segments in a craniocaudal sequence
involves two mechanisms: clock and wavefront model
wavefront
first step of somitogenesis; associated with the elongation of the caudal end of the body through proliferative activity of mesenchymal cells in the most posterior nonsegmented part of the primitive streak
divide most actively through FGF-8
more anteriorly where cells are older, [FGF-8] decreases
cells closer to the last-formed somite become exposed to increasing concentrations of retinoic acid, which is produced in the most posterior somites and whose action opposes FGF-8
determination front: cross developmental threshold that prepares cells for entering the process of segmentation ; characterized by expression of Mesp-2 (prefigures a future somite)
the location of the wavefront extends caudally in the growing embryo, but it remains a constant distance from the last-formed somite pair
segmentation clock
next step; initiated in those presomitic cells that have passed over the previously mentioned threshold and are expressing Mesp-2
Notch, Wnt,, FGF pathways
lunatic fringe: concentrated at the future anterior border of the somite and c-hairy becomes concentrated along the future posterior border
anterior border is expressing ephrin receptor Eph A
posterior border expresses ephrin ligand ephrin B ; thus prevented from mixing and fissure forms between the two somites
Wnt-6 from the overlying ectoderm stimulated the expression of paraxis in the newly forming somite ; results in the transformation of mesenchymal cells of the anterior part of the somite into an epithelial cell type
somite undergoes an internal subdivision into anterior and posterior halves; significant in forming vertebrae
paraxis
transcription factor that causes the complete transformation of segmented blocks of mesenchymal cells into a sphere of epithelial cells
somitocoel
small central lumen, contains a few core cells; apical surfaces of epithelial somite surround the somitocoel ;
outer basal surface of somites surrounded by basal lamina
sclerotome
ventral half of the somite; shh and noggin from notochord and the ventral wall of the neural tube cause scelrotoe to express Pax1 and Pax9
leads to a burst of mitosis and loss of N-cadherin, dissolution of basal lamina in the region and the transformation of the epithelial cells in the region back to a mesenchymal morphology (secondary mesenchyme)
chondroitin sulfate proteoglycans
produced by secondary mesenchymal cells as they migrate from the remainder of the somite; characteristic of cartilage matrix as secondary mesenchyme aggregates around the notochord
dermomyotome
dorsal half of the epithelial somite; expresses its own characteristic genes (Pax3, Pax7, paraxis)
myotome
mesenchymal cells arising from the dorsomedial and ventrolateral borders of the dermomyotome form this separate layer beneath the remaining somatic epithelium (dermatome)
produce muscle, and the cells of the dermatome contribute to the dermis
sclerotome derivatives
ventral: vertebral bodies and their intervertebral disks
lateral: distal ribs, some tendons
dorsal: dorsal part of neural arch, spinous process
central: pedicles and ventral parts of neural arches, proximal ribs, or transverse processes of vertebrae
medial (meningtome): meninges and blood vessels of meninges ; medial edge; surround the developing spinal cord
arthrotome derivatives
intervertebral disks, vertebral join surfaces, proximal ribs
cells from the somitocoel
dermatome derivatives
dermis, blade of scapula
myotome derivatives:
dorsomedial: intrinsic back muscles (epaxial)
ventrolateral: limb muscles or muscles of ventrolateral body wall (hypaxial)
neurotome derivatives
endoneurial and perineurial cells
syndetome derivatives
tendons of epaxial musculature
produce scleraxis (TF found in tendons)
conditions for myogenesis in the dorsomedial sector of the dermomyotome
noggin inhibits ectodermally produced BMP-4 (inhibits myogenesis)
these cells stop producing pax-3 and pax-7 and begin to express myogenic regulatory molecules such as MyoD and Myf-5
ventrolateral sector of the dermomyotome signaling molecules
influence of BMP-4 (produced by lateral plate mesoderm)
no myogenic factors expressed; cells continue expressing Pax-3; also produce receptor molecule c-met
scatter factor (hepatic growth factor) growth factor secreted in the region of limb buds, binds to the c-met receptor of the dermomyotome, stimulating these cells to migrate out of the somite and into the limb bud even before the myotome forms
continue to express Pax-3 and N-cadherin while migrating
posterior sclerotome
these cells multiply at a greater rate than do those of the anterior part, resulting in higher cellular density in the posterior sclerotome
do not permit the passage of either outgrowing nerve fibers or neural crest cells
neurotome
anterior sclerotome; outgrowing neural structures can only pass through the anterior end of the sclerotome
vertebra formation
cells of he anterior half of one somite aggregate with cells of the posterior half of the more cranial somite, forming a single vertebra
places bony vertebrae out of phase with the myotomally derived segmental muscles of the trunk, allowing the contracting segmental muscles to move the vertebral column laterally
intermediate mesoderm
connects to the paraxial mesoderm and the lateral plate mesoderm; runs along the entire length of the trunk
appears to arise as a response of the early mesoderm to BMP, secreted by lateral ectoderm and activin and other signals from paraxial mesoderm
Pax-2 expressed here
cranial border established by Hox-4 and caudal border by Hox-11
precursor of the urogenital system– pronephros and pronephric duct appear here
lateral plate mesoderm
ectoderm overlying lateral plate mesoderm produces BMP-4 which causes mesoderm to produce BMP-4
divides into two layers: dorsal layer=somatic mesoderm and combination of somatic mesoderm and ectoderm is somatopleure
ventral layer=splanchnic mesoderm and is closely associated with the endoderm (splanchnopleure) and specified by transcription factor Foxf-1
formation of the coelom
begins to form as the embryo undergoes lateral folding; at first intraembryonic coelom is continuous with extraembryonic coelom, but when folding complete, two spaces are separated
in cylindrical embryo, somatic mesoderm is the lateral and ventral body wall; splanchnic mesoderm forms the mesentery and wall of digestives tract
extraembryonic mesoderm
continuous with splanchnic and somatic mesoderm;
posterior end of the embryo is connected with the trophoblastic tissues by the mesodermal body stalk
body stalk will eventually become the umbilical cord
early development of the circulatory system:
migration of heart forming cells arising in the epiblast through the primitive streak in a well-defined anteroposterior order
cells passing through the streak closest to the primitive node form the outflow tract,, cells passing through the midstreak form the ventricles and cells that form the atria enter the streak most posteriorly
Nkx2-5, MEF2 and GATA4 important to heart development
cardiogenic mesoderm or cardiac crescent
after leaving primitive streak, associated with splanchnic mesoderm, become arranged in the same order in a U-shaped region of the cardiogenic mesoderm
cells from here form the left ventricle, most of the atria, and make minor contributions to the outflow tract and the right ventricle
secondary (anterior) heart field
located in the splanchnic mesoderm on the posteromedial side of the cardiac crescent;
anterior cells form most of the outflow tract and the right ventricle while those from the posterior part form the atria
myocardial primordium
thickened main layer of the splanchnic mesoderm in the precardiac region
endocardial primordia
isolated mesodermal vesicles between the myocardial primordium and the endoderm of the primitive gut that fused; will eventually form the inner lining of the heart
structure of the primitive tubular heart
inner endocardial lining surrounded by a loose layer of specialized ECM called cardiac jelly
outside cardiac jelly is myocardium and then the epicardium and fibroblasts within the heart muscles derived from proepicardial primordium
entire heart located in the space called pericardial coelom
soon after it is formed, the heart begins to form the characteristic S-shaped loop
Cell lineages of the early heart
N-cadherin-positive cells go on to form either atrial or ventricular myocytes
N-cadherin-negative cells form the endocardial lining and later cells of endocardial cushions
modified atrial and ventricular cardiac myocytes form the cells of the cardiac conduction system
heart begins beating by 22 or 23 days after fertilization
blood islands
formed in the extraembryonic splanchnic mesoderm of the yolk sac; have hemangioblast stem cells
inductive signal: indian hedgehog;; yolk sac mesoderm responds by producing BMP-4
central blood forming cells as hemocytoblasts and the outer cells become endothelial lining cells which form the inner walls of blood vessels
blood islands that fuse become primitive vascular channels that extend toward the body of the embryo
gut formation
[read over pages 107-110]
don’t really need to know the details that well
intraembryonic circulatory arc
ventral aortic outflow tract from the heart splits into a series of aortic arches passing around the pharynx through the pharyngeal arches and then collecting into a cephalically paired dorsal aorta that distributes blood throughout the body
retained as vessels or ligaments in the adult body
vitelline or omphalomesenteric arc
principally an extraembryonic circulatory loop that supplies the yolk sac
does not persist after birth
umbilical vessels arc
extraembryonic; course through the body stalk and spread in an elaborate network in the placenta and chorionic tissues; real lifeline between the embryo and he mother
does not persist after birth
