Chapter 4: Molecular Basis for Embryonic Development

Question 1

transcription factors

Answer 1

proteins possessing domains that bind to the DNA of promoter or enhancer regions of specific genes

also possess domain that interacts with RNA polymerase II or other transcription factors and consequently regulates the amount of mRNA produced by that gene

some are general that can be found in virtually all cells while others are extremely specific for certain types of cells and stages of development

Question 2

signaling molecules

Answer 2

leave the cells that produce them and exert their effects on others, which can be neighboring cells or cells located at greater distances

many are members of the growth factor family

signaling molecules bind as ligands to receptor molecules that are often transmembrane proteins protruding through the plasma membrane of cells that they affect

Question 3

signal transduction pathway

Answer 3

set off by the formation of a signaling molecule-receptor molecule complex; result in cascade of events that transmits the molecular signal to the nucleus of the responding cell

Question 4

homeodomain proteins

Answer 4

contain a highly conserved homeodomain region of 60 amino acids

homeodomain: type of helix-loop-helix region

Question 5

homeobox

Answer 5

the 180 nucleotides in the gene that encode the homeodomain

Question 6

maternal effect genes

Answer 6

in Drosophila, establish the dorsoventral and anteroposterior axes of the embryo

Question 7

gap genes

Answer 7

control the first step of segmentation in Drosophila; subdivide the embryo into broad regional domains

Question 8

pair-rule genes

Answer 8

control the second step of segmentation in Drosophila; involved in the formation of seven pairs of stripes along the craniocaudal axis of the embryo

Question 9

segment-polarity genes

Answer 9

control the third step of segmentation in Drosophila; work at the level of individual segments and are involved in their anteroposterior segmentation

Question 10

homeotic genes in Drosophila

Answer 10

impart specific or regional characteristics to the newly formed segments;

found in the antennapedia complex and the bithorax complex

Question 11

antennapedia-bithorax complex in Drosophila

Answer 11

consists of 8 homeobox-containing genes located in 2 clusters on the chromosome

mice and humans have at least 39 homologous homeobox genes

Question 12

vertebrate Hox genes

Answer 12

paly a prominent role in craniocaudal segmentation of the body and their spatiotemporal expression proceeds according to very regular rules

genes are activated and expressed according to a strict sequence in the 3’ to 5’ direction

originally described to operate along the main body axis;; later discovered to be involved in developing organs or regions such as the gut, limbs, and internal and external genitalia

Question 13

loss-of-function mutations

Answer 13

result in posterior-to-anterior transformations (cells of a given segment form the structural equivalent of the next most anterior segment)

Question 14

gain-of-function mutations

Answer 14

result in anterior-to-posterior structural transformations (cells of a given segment form the structural equivalent of the previous most posterior segment)

Question 15

Pax gene family

Answer 15

consists of 9 known members;

homologous to Drosophila pair-rule segmentation genes

all contain a paired domain of 128 amino acids that bind to DNA;; some also contain entire or partial homeobox domains and conserved octapeptide sequence

play important role in sense organs and developing nervous system; also involved in cellular differentiative processes when epithelial-mesenchymal transition occurs

Question 16

POU gene family

Answer 16

Pit1: gene uniquely expressed in the pituitary

Oct1 and Oct2; Oct4 plays important role in early cleavage

Unc86: expressed in nematode

contain a homeobox, region encoding 75 amino acids, which also bind to DNA through a helix-loop-helix structure

Question 17

Lim proteins

Answer 17

large family of homeodomain proteins; some bind to DNA in the nucleus and others are localized in the cytoplasm

involved in some stage of formation of virtually all parts of the body

no Lim=headless mammal

Question 18

Dlx gene family

Answer 18

group of genes that have been phylogenetically conserved; six members

play important role in patterning, especially outgrowing structures, in early embryo

operate in pairs which are closely associated with Hox genes

involved in morphogenesis of jaws and inner ear and in early development of the placenta

Question 19

Msx genes

Answer 19

small, highly conserved family of homeobox-containing genes; only two in humans;

play important roles in embryonic development; especially in epitheliomesenchymal interactions in the limbs and face

generally inhibitors of cell differentiation in prenatal development

in postnatal life; maintain proliferative capacity of tissues

Question 20

T-box (tbx) gene

Answer 20

takes name from brachyury (T) locus; recognized originally to cause short tails in heterozygotic mice

involved in development, with roles such as inducing the mesodermal germ layer, and coordinating outgrowth or either the arm or the leg

Question 21

basic helix-loop-helix proteins

Answer 21

contain a short stretch of amino acids in which two alpha-helices are separated by an amino acid loop

helices region (with adjacent basic regions) allows the regulator protein to bind to specific DNA sequences

Question 22

forkhead (Fox) genes

Answer 22

family of transcription factors

contain a winged helix structure; expressed in many developing organs throughout the body; tend to have microscopically distinct domains within the developing organ and can work together to direct the morphogenesis of a structure

Question 23

zinc finger transcription factors

Answer 23

proteins with regularly placed cystidine and histidine units that are bound by zinc ions and cause he polypeptide chain to pucker into fingerlike structures which can then be inserted into specific regions of the DNA helix

Question 24

Sox genes

Answer 24

large family that have in common HMG domain

SRY gene is one example;

work in concert with other transcription factors to influence the expression of their target genes

Question 25

HMG (high mobility group) domain

Answer 25

found on Sox genes; unusually for a transcription factor in that, with a partner protein, it binds to 7 nucleotide on the minor instead of the major groove on the DNA helix and causes a pronounced conformational change in the DNA

Question 26

WT1 gene

Answer 26

isolated gene that in prenatal life plays a prominent role in formation of both the kidneys and the gonads

crucial for the development of early forms of kidney and for formation of definitive adult kidney; necessary for formation of the gonads

Question 27

transforming growth factor-beta family

Answer 27

numerous molecules that play a wide variety role during embryogenesis and postnatal life

regulated by several molecules that bind to them in the extracellular space

Question 28

TGF-beta 1-5

Answer 28

mesodermal induction
myoblast proliferation
invasion of cardiac jelly by atrioventricular endothelial cells

Question 29

activin

Answer 29

granulosa cell proliferation

mesodermal induction

Question 30

inhibin

Answer 30

inhibition of gonadotropin secretion by hypophysis

Question 31

Mullerian inhibiting substance

Answer 31

regression of paramesonephric ducts

Question 32

decapentaplegic

Answer 32

signaling of limb development

Question 33

Vg1

Answer 33

mesodermal and primitive streak induction

Question 34

BMP-1 to BMP-15

Answer 34

induction of neural plate, induction of skeletal differentiation, and other inductions

exert their effects by inhibiting other processes in the embryo

Question 35

nodal

Answer 35

formation of mesoderm and primitive streak, left-right axial fixation

Question 36

glial cell line-derived neurotrophic factor

Answer 36

induction of outgrowth of ureteric bud, neural colonization of gut

Question 37

lefty

Answer 37

determination of body asymmetry

Question 38

fibroblast growth factor family

Answer 38

play important roles in a variety of phases of embryonic development and in fulfilling functions, such as stimulation of capillary growth, post natal body

mainly regulated farther downstream; secreted FGFs are closely associated with extracellular matrix and must bind to heparan sulfate to activate their receptors

Question 39

means of regulating FGF

Answer 39

modification of their interaction with heparan proteoglycans in the receptor complex

regulation at the membrane of the responding cell through the actions of transmembrane proteins

intracellular regulation by molecules, such as SPROUTY, which complex with parts of the signal transduction machinery of the responding cell

Question 40

hedgehog family and sonic hedgehog

Answer 40

protein with highly conserved N-terminal region and a more divergent C-terminal region

after its synthesis and release from RER, the signaling peptide is cleaved off and glycosylation occurs on the remaining peptide;

still within the cell, shh peptide undergoes autocleavage through the catalytic activity of its C-terminal portion, while the N-terminal segment becomes covalently bonded with cholesterol

the N-terminal peptide is secreted from the cell, but it remains bound to the surface off the cell that produced it;; all the signaling activity of shh resides in the N-terminal segment
through the activity of another gene product, the N-terminal segment of shh, still bound to cholesterol is released from the cell;

C-terminus plays no role in signaling

Question 41

shh signaling pathway on target cell

Answer 41

shh, still with cholesterol, binds to Patched (Ptc) receptor, closely associated with transmembrane smoothened (smo)

Ptc normally inhibits smo, but shh inhibits Ptc, thus allowing smo to give off intracellular signal

Question 42

Wnt family

Answer 42

plays dramatically different roles in different classes of vertebrates; in mammals, plays important role during gastrulation (stimulate cellular proliferation that is required to bring organs to their normal proportions)

often interact with components of the ECM;

Wnt-inhibitory factor-1 (WIF-1) and Cerberus directly bind to the Wnt molecule, inhibiting it

dickkopf effect inhibition by binding to receptor complex

Question 43

chordin, noggin, gremlin

Answer 43

inhibit activity of BMP, which itself is an inhibitor

inhibiting the inhibitor a common trend in developmental biology signaling molecules

Question 44

positive and negative regulators of growth

Answer 44

positive: shh and FGF
negative: some BMP

Question 45

cell surface receptors

Answer 45

typically transmembrane proteins with extracellular, transmembrane and cytoplasmic domains

extracellular domain has a binding site for the ligand; binding of ligand affects conformational change in the cytoplasmic domain

two main types: (1) intrinsic protein kinase activity and (2) receptors that use a secondary messenger system to activate cytoplasmic protein kinases

Question 46

lateral inhibition

Answer 46

when one cell from a group of developmentally equivalent cell differentiates into a dominant mature cell type and signals its subservient neighbors to prevent them from differentiating into the same cell type

Question 47

Notched signaling pathway

Answer 47

common mechanism of lateral inhibition

cell surface receptor with a large extracellular domain and a smaller intracellular domain

becomes activated when combines with ligands Delta or Jagged that extend from the surface of the dominant cell, setting off pathway that inhibits the neighboring cell from differentiating into the dominant phenotype

complexing of Notch with ligand stimulates an intracellular protease reaction that cleaves off the intracellular domain of the Notch molecule

intracellular domain translocated to nucleus; on the way becomes associated with regulatory proteins such as deltex;

in the nucleus, intracellular domain of Notch combines with several helix-loop-helix transcription factors and complex binds to DNA of gene called enhancer of split

product of enhancer of split is a transcription factor that regulates other genes

Question 48

signal transduction

Answer 48

process by which signal provided by the first messenger is translated into an intracellular response

binding of signaling molecule to receptor resulting in a conformational change of the receptor

sets of chain reaction that carries the signal to the nucleus, where it ultimately influences gene expression

Question 49

receptor tyrosine kinase (TRK) pathway

Answer 49

members of FGF family do this

FGF binds to receptor, G protein near receptor becomes activated and results in RAS ==> RAF ==> MAP kinase ==> ERK which enters nucleus and phosphorylates transcription factors

Question 50

TGF-beta and Smad proteins

Answer 50

TGF-beta binds to type II serine-threonine kinase receptor which complexes with type I receptor

two different Smad proteins, R-Smad and Co-Smad dimerize and enter the nucleus; binds with cofactor and is then capable of binding with some regulatory element on DNA

Question 51

Wnt pathway

Answer 51

binding of Wnt to transmembrane receptor, Frizzled,

Frizzled interacts with Disheveled, which ties up a complex of numerous molecules (destruction complex) which in the absence of Wnt causes the degradation of beta-catenin

if beta-catenin is not destroyed, it enters the nucleus where it acts as a powerful adjunct to transcription factors that determine patterns of gene expression

Question 52

Hippo pathway

Answer 52

regulates the growth of organs throughout the animal kingdom

Question 53

small RNAs

Answer 53

small noncoding RNA molecules that exert an enormous array of influence on gene expression, mainly at posttranscriptional levels

can be divided into two groups: those that act during gametogenesis and those that act during embryogenesis

gametogenesis: Piwi-interacting RNAs (piRNAs) important in spermatogenesis and endogenous small interfering RNAs (endo-siRNAs) play vital roles in oogenesis

miRNAs expressed in somatic tissues during embryonic development

Question 54

vitamin A (retinol) and its metabolite, retinoic acid

Answer 54

retinol binds to retinol-binding protein, which attaches to specific cell surface receptors

retinol then released and binds to cellular retinol binding protein (CRBP I); all-trans retinol then converted into all-trans retinoid

CRBP I and CRABPI (cellular retinoic acid-binding protein) regulate the amount of retinoids that enter the nucleus

retinoic acid enters the nucleus when released from CRABP and binds with dimer heterodimer retinoic acid receptor (RAR), retinoid X receptor (RXR)

this complex then binds to retinoic acid response element (RARE) on DNA in the enhancer region of a gene