Chapter 6: Establishment of the Basic Embryonic Body Plan

Question 1

neural plate

Answer 1

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

Question 2

convergent extension

Answer 2

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

Question 3

neural groove and third stage of neurulation

Answer 3

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

Question 4

median hinge point

Answer 4

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

Question 5

lateral hinge point

Answer 5

[see Fig. 6-2, pg. 94]

forms as a result of apical constriction of cells in a localized area

Question 6

fourth stage of neurulation

Answer 6

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

Question 7

anterior and posterior neuropores

Answer 7

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

Question 8

secondary neurulation

Answer 8

occurs in mammals that have tails

Question 9

segmentation of the neural tube vs. segmentation of somites

Answer 9

segmentation by subdivision of an existing structure (neural tube)

segmentation by adding terminal segments (somites)

Question 10

three-part brain and its structures

Answer 10

prosencephalon (forebrain) –> telencephalon and diencephalon

mesencephalon (midbrain)

rhombencephalon (hindbrain) —> metencephalon and myelencephalon

Question 11

neuromeres

Answer 11

neuromeres: certain regions of the brain are subdivided into transiently visible series of regular segments

rhombencephalon divided into rhombomeres and prosencephalon into prosomeres

Question 12

rhombomeres

Answer 12

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

Question 13

segmentation of the neural tube

Answer 13

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

Question 14

isthmic organizer

Answer 14

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

Question 15

anterior neural ridge

Answer 15

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

Question 16

zona limitans

Answer 16

shh-secreting group of cells that organize the border between the future dorsal and ventral thalamus

Question 17

rhombomere segmentation and genes involved

[see Fig. 6-4, pg. 96]

Lecture Notes Diagram

Answer 17

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

Question 18

ephrins

Answer 18

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)

Question 19

segmentation of spinal cord

Answer 19

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

Question 20

neural crest

Answer 20

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”)

Question 21

ectodermal placodes

Answer 21

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

Question 22

paraxial mesoderm (segmental plate)

Answer 22

lateral to the neural plate; homogenous strip of closely packed mesenchymal cells

becomes organized into somites

somitomeres found in paraxial mesoderm;

Question 23

somites

Answer 23

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

Question 24

first seven somitomeres

Answer 24

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

Question 25

somitogenesis

Answer 25

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

Question 26

wavefront

Answer 26

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

Question 27

segmentation clock

Answer 27

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

Question 28

paraxis

Answer 28

transcription factor that causes the complete transformation of segmented blocks of mesenchymal cells into a sphere of epithelial cells

Question 29

somitocoel

Answer 29

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

Question 30

sclerotome

Answer 30

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)

Question 31

chondroitin sulfate proteoglycans

Answer 31

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

Question 32

dermomyotome

Answer 32

dorsal half of the epithelial somite; expresses its own characteristic genes (Pax3, Pax7, paraxis)

Question 33

myotome

Answer 33

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

Question 34

sclerotome derivatives

Answer 34

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

Question 35

arthrotome derivatives

Answer 35

intervertebral disks, vertebral join surfaces, proximal ribs

cells from the somitocoel

Question 36

dermatome derivatives

Answer 36

dermis, blade of scapula

Question 37

myotome derivatives:

Answer 37

dorsomedial: intrinsic back muscles (epaxial)
ventrolateral: limb muscles or muscles of ventrolateral body wall (hypaxial)

Question 38

neurotome derivatives

Answer 38

endoneurial and perineurial cells

Question 39

syndetome derivatives

Answer 39

tendons of epaxial musculature

produce scleraxis (TF found in tendons)

Question 40

conditions for myogenesis in the dorsomedial sector of the dermomyotome

Answer 40

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

Question 41

ventrolateral sector of the dermomyotome signaling molecules

Answer 41

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

Question 42

posterior sclerotome

Answer 42

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

Question 43

neurotome

Answer 43

anterior sclerotome; outgrowing neural structures can only pass through the anterior end of the sclerotome

Question 44

vertebra formation

Answer 44

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

Question 45

intermediate mesoderm

Answer 45

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

Question 46

lateral plate mesoderm

Answer 46

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

Question 47

formation of the coelom

Answer 47

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

Question 48

extraembryonic mesoderm

Answer 48

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

Question 49

early development of the circulatory system:

Answer 49

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

Question 50

cardiogenic mesoderm or cardiac crescent

Answer 50

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

Question 51

secondary (anterior) heart field

Answer 51

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

Question 52

myocardial primordium

Answer 52

thickened main layer of the splanchnic mesoderm in the precardiac region

Question 53

endocardial primordia

Answer 53

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

Question 54

structure of the primitive tubular heart

Answer 54

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

Question 55

Cell lineages of the early heart

Answer 55

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

Question 56

blood islands

Answer 56

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

Question 57

gut formation

Answer 57

[read over pages 107-110]

don’t really need to know the details that well

Question 58

intraembryonic circulatory arc

Answer 58

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

Question 59

vitelline or omphalomesenteric arc

Answer 59

principally an extraembryonic circulatory loop that supplies the yolk sac

does not persist after birth

Question 60

umbilical vessels arc

Answer 60

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