Study Guide

Front 1

how are neural cells specified

Back 1

1. competence - cells will become neuroblasts if they are exposed to appropriate signals
2. specification - progression can still be repressed by other signals
3. commitment - will become neurons even with inhibitory signals
4. differentiation - neuroblasts leave the mitotic cycle and express neuron genes

Front 2

how is the central nervous system constructed

Back 2

primary neurlation - divides original ectoderm into internally positioned neural tube, externally positioned epidermis, and neural crest cells

secondary neurulation - production of mesenchyme cells from prospective ectoderm and endoderm, and then the condensation of these cells into the medullary cord

Front 3

what are the steps to primary neurulation

Back 3

Formation of the neural plate - dorsal mesoderm tells ectodermal cells to elongate into neural plate cells and they extend along the AP axis

binding and convergence of the neural plate - plate bends at midline forming medial hinge point (MHP) and become anchored to the notochord. Two other hinges called the dorso-lateral hinge points (dlhp) form and are anchored to the ectoderm

closure of the neural tube - neural folds are brought together and adhere, these cells become the neural crest. neural tube forms closed cylindar and separates mediated by N-cadherin and N-cam

Front 4

how does the brain form

Back 4

neural tube cells differentiate
brain neurons differentiate
tissue of the cns is re-architectured
the cerebellum is organized
the cerebrum is organized

Front 5

how is the neural tube differentiated

Back 5

neural tube and lumen bulge and constrict to form the chambers of the brain and spinal cord

cells rearrange into diff. functional regions of the brain and spinal cord

neuroepithelial cells differentiate into the numerous types of neurons and glia

Front 6

what is the AP axis of the brain

Back 6

neural tube ballons into the forebrain, midbrain, and hindbrain

FOREBRAIN
-optic vesicles that become retina extend laterally from each side
-Telencephalon -> cerebrum
-Diencephalon -> retina, thalamic, hypothalamic

HINDBRAIN
->myelencephalon -> medulla oblongata
-metencephalon -> cerebellum
-rhombomeres + neural crest cells -> ganglia

Front 7

DV axis of the brain
-how is it induced

Back 7

-induced by signals coming from its immediate environment
-Shh from the notochord induces ventral side MHP cells to become floor plate of neural tube and they secrete shh
-dorsal ectoderm uses TGF-B to signal dorsal cells of the neural tube to become roof plate cells that express BMP4

Front 8

how are the ventricles of the brain induced

Back 8

shaped by regional differences in cell proliferation and adhesion

Front 9

how is the spinal cord and the medulla organized

Back 9

neural tube cells migrate into three zones:
1. intermediate zone
-> becomes gray matter
2. the ventricular zone
3. the marginal zone
-> becomes white matter

Gray matter becomes butterfly shaped and is surrounded by white matter

a longitudinal groove called the sulcus limitans, divides the neural tube into dorsal (sensory) and ventral (motor) halves

Front 10

how is the cerebellum organized

Back 10

some neuronal precursors enter the marginal zone to form nuclei

some neuronal precursors migrate to the outer surface and form the external granular layer near the outer boundary of neural tube. granular cells migrate along bergmann glia via adhesion protein called astrotactin

outermost external granular cells are specified with BMPs and they become Granule cell neurons

granule cell neurons migrate back toward the ventricular zone to form the internal granular layer

ventricular zone of cerebellum generates purkinje glial neurons that secrete shh to sustain division of granular cells

Front 11

how is the cerebrum organized

Back 11

neocortex is specified via Ihx2 and become six layers of neuronal cell bodies

Front 12

what are the steps to development of the vertebrate eye

Back 12

1. optic vesicle extends toward the surface ectoderm from the forebrain
2. the lens placode appears as a local thickening of the surface ectoderm near the optic vesicle
3. lens placode enlarges and the optic vesicle forms an optic cup
4. the central portion of the lens forming ectoderm invaginates while the two layers of the retina are distinguished
5. lens vesicle forms
6. lens consists of anterior epithelial cells and posterior fiber cells
7. the cornea develops in front of the lens

Front 13

what signals are involved in the formation of the eye field

Back 13

the anterior portion of the neural tube expresses Otx2 gene and ET protein

ET controlls Rx

Rx inhibits Otx2 and activates Pax6 allows for the activation of genes that form the eye field

shh is needed to split the eye field into bilateral fields

Front 14

how are neural retinal cells differentiated

Back 14

BMP from dorsal regions and shh from ventral regions

ventral cells express pax2 and become optic stalk

dorsal cells express MITF and become pigmented epithelium

Central bulge expresses Rx and becomes the optic cup

retinal neurons are specified by Pax6 and Six3

Xotx5b specifies photoreceptor neurons

Xotx2 and Xvsx1 specify bipolar neurons

Front 15

how are lens and cornea cells differentiated

Back 15

sox2 and pax6 txn factors bind close together on a small region of the crystalline enhance.. causes lens to generate

Front 16

how is the ability to produce lens tissue induced?

Back 16

1. foregut endoderm
2. cardiac mesoderm
3. anterior neural plate
4. Pax6 in anterior ectoderm
5. Optic vessicle (BMP4, FGF8)

Front 17

how does the epidermis form

Back 17

ectodermal cells covering the embryo after neurulation are specified by BMPs to become epidermis

BMPs activate p63 which leads to keratinocyte proliferation and differentiateion -> stimulates the production of notch ligand Jagged. jagged activates keratinocyte differentiation

Front 18

how do cutaneous appendages form

Back 18

Reciprocal inductive interactions between the dermal mesenchyme and the ectodermal epithelium lead to the formation of epidermal placodes (thickened epidermis at the base precursor of hair follicles). Cells in the regions that form placodes secrete wnt.

Aggregation of cells in the basal layer of the epidermis occurs and is directed by the underlying dermal fibroblast cells. Dermal fibroblast cells respond to the ingression of epidermal cells by forming a small node or dermal papilla. Dermal papill pushes up on basal stem cells which causes them to divide more rapidly. The daughter cells differentiate into keratinized hair shaft

Patterning is due to reaction-diffusion based on competition between placode promoting factors (Wnts) and inhibitors (dickkopf). In one such regulatory loop, Wnt activates expression of its own inhibitor, Dkk4, in placodes. As Dkk4 is thought to be more diffusible than Wnt ligands, it may suppress pla-code fate in cells adjacent to the placode, thereby contribut-ing to patterning

Front 19

how do hair follicles form

Back 19

Signals initiate local proliferation of the basal keratinocytes in the epidermis. Proliferation of epidermal cells results in formation of the hair follicle placode, which signals the dermal mesenchymal cells to aggregate beneath it into a dermal papilla. The papilla signals the proliferation of the hair germ, making it into a primitive hair shaft ( or “ hair peg”). The hair shaft engulfs the dermal papilla and forms the inner hair root directly above the papilla. Sebaceous cells ( sebocytes) and the bulge appear as melanin granules enter into the cortex. Sebaceous glands form, and the hair canal is made. The hair shaft differentiates the inner root sheath of epidermal cells. The sebaceous gland is localized on the lateral wall of the follicle, while the hair shaft extends into the hair canal and out past the skin.

Front 20

how are muscles made

Back 20

• myotome cells are determined by paracrine factors. committed myoblasts divide in the presence of growth factors (fgfs) but show no obvious muscle-specific proteins. when growth factors are all used up, the myoblasts cease dividing, align with eachother, fuse into myotubes. myotubes become organized into muscle fibers that spontaneously contract.

Front 21

how are bones made

Back 21

• Endochondral = Mesenchymal cells commit to becoming cartilage cells ( chondrocytes). ( B) Committed mesenchyme condenses into compact nod-ules. ( C) Nodules differentiate into chondrocytes and proliferate to form the cartilage model of bone. ( D) Chondrocytes undergo hypertrophy and apoptosis while they change and mineralize their extracellular matrix. ( E) Apoptosis of chondrocytes allows blood vessels to enter. ( F) Blood vessels bring in osteoblasts, which bind to the degenerating cartilaginous matrix and deposit bone matrix. ( G) Bone formation and growth consist of ordered arrays of proliferating, hypertrophic, and mineral-izing chondrocytes. Secondary ossification centers also form as blood vessels enter near the tips of the bone
• Intramembranous = Bone formation directly from mesenchyme. There are three main types of ______ bone: sesamoid bone and periostal bone, which come from mesoderm, and dermal bone which originate from cranial neural crest- derived mesenchymal cells.

Front 22

how do tendons form

Back 22

• myotome secretes FGF onto the sclerotome. sclerotome in the presence of fgf secretes scleraxix which activates tendon genes.
• sclerotome in the presence of shh (from the notochord and the floorplate) secretes sox 9, which activates sox5 and sox6, which activate cartilage genes and inactivate scleraxis. shh also inhibits scleraxis
• the tendons associate with muscles directly above them and with the skeleton

Front 23

how do metanephric kidneys form

Back 23

• The original tubules, constituting the pronephros, are induced from the nephrogenic mesenchyme by the pronephric duct as it migrates caudally. ( B) As the pronephros degenerates, the mesonephric tubules form. ( C) The final mammalian kidney, the metanephros, is induced by the ureteric bud, which branches from the nephric duct
• As the ureteric bud enters the metanephrogenic mesenchyme, the mesenchyme induces the bud to branch. ( B– G) At the tips of the branches, the epitheli-um induces the mesenchyme to aggregate and cavitate to form the renal tubules and glomeruli ( where the blood from the arteriole is fil-tered). When the mesenchyme has condensed into an epithelium, it digests the basal lamina of the ureteric bud cells that induced it and connects to the ureteric bud epithelium. A portion of the aggre-gated mesenchyme ( the pretubular condensate) becomes the nephron ( renal tubules and Bowman’s cap-sule), while the ureteric bud becomes the collecting duct for the urine.

Front 24

what signals are critical for kidney development

Back 24

• paraxial mesoderm signals to the intermediate mesoderm
• intermediate mesoderm is signaled to become intermediate mesoderm by the BMP gradient
• paraxial mesoderm secretes lim1, pax2 and pax8 that signal the intermediate mesoderm to form the kidney

Front 25

how is the limb bud specified

Back 25

• Fgf8 is eliminated from areas that will form limb buds due to retinoic acid secreted by somites. where there is no Fgf8 secreted by the somites, paracrine factor Fgf10 is secreted by the lateral plate mesoderm cells that will become the prospective limb skeleton. the signal initiates the limb forming interactions between ectoderm and mesoderm. Fgf10 expression is stabilized by actions of Wnt proteins

Front 26

how is the AV axis established and coordinated in limb formation

Back 26

• Av = a small block of mesoderal tissue near the posterior junction of the young limb bud and the body wall called the zone of polarizing activity, where shh is expressed. the side of the limb bud expressing shh will become the posterior or pinky side of the arm

Front 27

how is the DV axis established and coordinated in limb formation

Back 27

= dorsal-ventral or knuckles-palms determined by the ectoderm encasing the limb bud. wnt7a gene is expressed in the dorsal ectoderm of limb buds. wnt7a activates lim1 gene in dorsal mesenchyme. lim1 encodes txn factor that specifies dorsal cells fates in the limb

Front 28

how is the PD axis established and coordinated in limb formation

Back 28

• positional information for proximal-distal polarity is in the mesenchyme. the limb bud becomes sequentially patterned into three areas. In the first area, basically the progress zone, cells respond to FGFs from the AER that suppress the synthesis of fibronectin and thereby prevent condensation of the mesenchyme cells into car-tilaginous nodules. In the area just beyond the reach of the AER signals, each mesenchymal cell becomes responsive to TGF- ß signals produced by other mesenchymal cells and by themselves. This is the region of patterning activity that directs the formation of cartilaginous nodules. TGF- ß acts ( 1) as a positive inducer of itself, ( 2) as a positive inducer of the extracellular matrix protein fibronectin ( which induces cartilaginous nodule forma-tion), and ( 3) as an inducer of its own soluble inhibitor ( which has not yet been identified). This signaling creates a periodic pattern of regions alternately containing and lacking TGF- ß and fibronectin. the form of each bone depen

Front 29

how are the major axis of the limb coordinated

Back 29

• when the limb bud is relatively small, an initial positive feedback loop between Fgf10 and Fgf8 is established. As the limb bud grows, the ZPAis established and anoth-er regulatory loop is created. Sonic hedge-hog in the ZPA activates Gremlin, which inhibits BMPs. The BMPs (mostly BMP4) are able to inhibit the FGFs of the AER. Thus, Sonic hedgehog in the ZPA prevents down-regulation of the FGF genes expressed in the AER: fgf4, fgf8, fgf9, and fgf17. relatively low levels of AER FGFs activate Shh and keep the ZPA functioning. The FGF signals repress the proteins Etv4 and Etv5, which are repressors of Sonic hedgehog transcription. the AER and ZPA mutually support each other through the positive loop of Sonic hedgehog and FGFs. In this phase of limb development, levels of Gremlin ( a powerful BMP antagonist) are high, and the positive FGF/ Shh loop sustains the limb growth. as FGF levels rise, they block Gremlin expression in the distal mesenchyme.

Front 30

how are joints made

Back 30

• BMP can be received int he presence of FGFs (to produce apoptosis) or Wnts (to induce bone). when fgfs from the AER are present, Dkk is activated. this protein mediates apoptosis and at the same time inhibits wnt from aiding in skeleton formation

Front 31

what are the major derivates of the endoderm

Back 31

• endoderm
->digestive tube
-->liver, gall bladder, pancreas, stomach, and respiratory tube
->respiratory tube -> lungs, pharynx, eustacian tubes, tonsils, thyroid, thymus, parathyroid glands, esophagus
-> also forms extraembryonic membranes like yolk sac and allantois

Front 32

how is the pancreas formed

Back 32

• from the hepatic diverticulum, a dorsal pancreatic bud forms the dorsal pancreas and a ventral pancreatic bud forms the ventral pancreas. the ventral pancreas migrates and fuses with the dirsal pancreas
• the notochord may actively promote pancreas formation while the heart blocks the pancreas from forming. lack of shh expression from notochord activates pancreas development.

Front 33

how is the liver formed

Back 33

• the developing heart and blood vessel endothelial cells (by secreting FGFs) induces the liver to form and the presence of the notochord inhibits liver formation. for the endoderm to respond to heart cell FGF signals, the endoderm becomes competent by the forkhead txn factors which open chromatin surrounding liver-specific genes

Front 34

what are the four extraembryonic membranes in mammals, and how do they support the life of the fetus?

Back 34

Chorion – gas exchange, placenta, immune and nutrition

amnion - protection

yolk sac - nutrients

allantois – nitrogenous waste