ANS 123 Quiz 3

Mesoderm differentiates during neurulation

• _______ ectoderm is still continuous w _______ ectoderm

• _______ present (beginning of neurelation)

  • primitive streak separates ectoderm into ______ & ______ allowing _______ below to differentiate into notochord formation

• Left & right sides of notochord = different plates of _______

• Epiblast , amnion

• Notochord

  • left & right sides, mesoderm

• mesoderm

Mesoderm differentiates during neurulation

• _______ mesoderm

  • Portion of mesoderm closest to notochord

  • on both sides of notochord, “hugging” notochord

• _______ mesoderm

  • Portion of mesoderm farthest from notochord

• Intermediate mesoderm

  • Portion of mesoderm between ______&______ mesoderm

• Paraxial

• Lateral

• paraxial & lateral

Mesoderm differentiates during neurulation

• Lateral, Intermed, Paraxial 

  • Further along in development, these sections of mesoderm _______ into _______ regions

    • Also important to note that the _______ plate mesoderm splits

  • Once separated, these regions ________ further

• separate, distinct regions

  • lateral

• differentiate

Mesoderm differentiates during neurulation

• Once separated, these regions differentiate further

  • _______ mesoderm

    • → head

    • → somite

  • _______ mesoderm

    • → kidney

    • → gonads

  • Lateral plate mesoderm

    • → __________ (dorsal, closest to eCTOderm)

    • → __________ (ventral, closest to eNDOderm)

• Paraxial

—

• Intermediate

—

• somatic mesoderm

• splanchnic mesoderm

Somites

• differentiated from _________ mesoderm

• the 1st ________ structure in embryo

• Influences _________ of body (key to correct body layout) & formation of _________ structures (ribs, vert, cranial/spinal nerves, muscles, etc.)

• May influence/trigger neural crest cell migration

• paraxial

• segmented

• regionalization, segmented

• neural crest cell

Somitogenesis

• Formation of somites 

  • occurs during primitive streak ________, & ________

  • Begins in _______ portion of embryo

• regression, neurulation

• anterior

Somitogenesis

• ________ mesoderm ”pinches‐ off” on each side of neural ______ & ________

  • →→ Paired blocks of _________

  • (1st separated from intermed mesoderm, then paraxial mesoderm itself separates into chunks that ea become somite)

• Somites form in ________ on either side of neural _______ & _______

  • 1. entire _______ mesoderm separates from ___________ mesoderm as 1 separated column / piece of ________ mesoderm

  • 2. once you have a whole thing of _______ mesoderm, then you start to chunk up the ________ mesoderm as you're gradually moving _________

  • 3. this chunking up creates the somites

• Paraxial, neural tube, notochord

  • paraxial mesoderm

  • (first separated from intermed mesoderm, then paraxial mesoderm itself separates into chunks that ea become somite)

• columns, neural tube, notochord

  • 1. paraxial, lateral plate, paraxial

  • 2. paraxial, paraxial, posteriorly

Somitogenesis

• Stages:

  • 1st visible somite pair , 4 somite pairs, 7 somite pairs, 10 somite pairs, etc…

  • as ____erior somites form, ____erior somites already doing job

    • that's why it's very difficult during devel to get an image w full range of intact somites anterior→posterior

    • wave of maturation anterior→posterior

• posterior

• anterior

Somites

• Each somite is very ________

• They then differentiate into 3 diff cell lineages:

  • __________ 

  • __________

  • __________

• multipotent

Each somite has 3 sections

1. Dermatome 

   • _______ most portion (closest to _____derm)

2. Myotome

   • __________ 

3. Sclerotome

   • _______ most portion (closest to _____derm)

Each section differentiates into _______ arranged mesodermal derivatives

• Dorsal, ectoderm

• Middle 

• Ventral most portion (closest to endoderm)

segmentally (segment)

• Each somite has 3 sections (dermatome, myotome, sclerotome)

• Each section differentiates into segmentally arranged mesodermal derivatives:

  • Dermatome  

    • →  ______ of ______

  • Myotome  

    • →  ________

  • Sclerotome

    • →  Axial ________ structures (______)

    • (becomes _______ of ________)

• Dermis of skin

• Muscles

• skeletal (bones)

  • bones of vertebral column

Somites

• Transverse v. Dorsal view

• Left pic = wedge shaped ________ on either side of notochord, can assume image is around time of ________

• Right pic = somites get numbered from ________ to ________ (anterior = more _______)

• somites, neuralation

• anterior → posterior ; mature

________ = How the embryo becomes 3D ( 2d → 3d )

body folding

Body folds

• Before folding:

  • Flat stanley / pancake

  • Flat ectoderm, flat mesoderm, flat endoderm 

  • Endoderm continuous w _______

• After folding:

  • close sides of 2D structure to create lateral __________ & enclose the ______/______

  • ________ (intraembryonic cavity) forms when ______ & ______ mesoderm separate (required for body folding)

• YSE

—

• body walls, gut tube / organs

• Coelom, somatic & splanchnic

Starting point of body folding

Body folds

• A) For body folding to occur, need to pinch definitive ________ away from ________ 

  • pinching & folding begins to occur on the side

  • effectively, pushing in on ______ of embryo

• definitive endoderm, YSE 

  • sides

Body folds

• B) Now, _______ mesoderm has split into 2 branches:

  • _______ mesoderm (track up around amnion)

  • _______ mesoderm (adhere to endoderm) 

• Creates gap as pinches even further; this larger gap eventually becomes _________ body cavity (_______) 

• lateral plate

  • somatic

  • splanchnic

• intraembryonic, coelom

Body folds

• C) Further along, ______ getting bigger, beginning to pinch off _________ 

• D) Further folding occurring; ______ getting pinched away from ______

• E) Completely folded; ______ no longer present (got pinched off); fully formed ______ (lined w cells that used to b definitive endoderm)

• gap, definitive endoderm 

• endoderm, YSE

• YSE, gut tube (definitive endoderm)

Body Folding 

• process of “pinching off” embryo from _____/_____

• In order:

  • 1. ________ fold (head fold)

  • 2. ________ body folds

  • 3. ________ fold (tail fold)

• As embryo’s body pinches off, _____&_____ fuse ventrally at midline

  • Incomplete _______ = hair lip, cleft palate

• Head region = more _______ than lower

• yolk/YSE

—

• 1. Subcephalic (head)

• 2. Lateral

• 3. Caudal (tail)

—

• right & left

  • fusing

• mature

Body Folding 

• Results:

  • 3D embryo “______” fused at ______

    • Marks off ________ from ________ region

    • Forms sides & ________ surface of embryo

  • ________ of embryo “tucked in”

• tube, midline

  • embryo proper, extra‐embryonic

  • ventral

• Germ layers

Heart Formation

• Heart formation = form of ___________

• In chicken, 1st heartbeats ~33‐38 hrs ___________

• _________ = well‐established by 51‐56 hrs

• Heart is formed along the way as _________ occurs

• organogenesis

• post‐fertilization

• Circulation

• body folding

Heart formation

• Prior to folding: ______ fills w _______ cells & _______ forms   

  • A) ________ still in process; ________ has fallen into ________; __________ is shoving hypoblast out of the way

  • B) _________ cells proliferate & fill up ________ w ________ cells; _______ ______ splits creating new cavity called _______

• blastocoel, mesoderm cells, coelom    

  • primitive streak - mesoderm , blastocele - definitive endoderm

  • B) mesoderm, blastocele, mesoderm cells - lateral plate mesoderm, coelom

Heart formation

• During regression: 

  • pre‐_______ ________ mesodermal cells get situated

    • 1. Migrate & merge _______ to _______ process

    • 2. _____________ cells undergo ________ & proliferate

• pre‐cardiac splanchnic

  • anterior, head process

  • Cardiac crescent cells, determination

Heart formation

• During regression: 

  • pre‐cardiac splanchnic mesodermal cells get situated

    • 1. Migrate & merge anterior to head process

      • have _____ & _____, proliferate/merge to create crescent

      • Cardiac crescent = 1^o ___________ (HFR) = ________ area

        

    • 2. Cardiac crescent cells undergo determination & proliferate

• right & left

• Heart field region , Cardiogenic

As embryo begins folding: early stages of formation of heart, foregut, coelom, & ventral body wall = interrelated

• 1. On each side of embryo, ________ mesoderm migrates ________

  • Coelom = space/cavity created when _____&_____ layers separate

• 2. Foregut forms as _______ migrates

  • ________ cells differentiate into _____cardial (heart) & ______cardial (vessels) precursor cells

• 3. Endocardial precursors form endocardial ______

• 4. Foregut closes → _______

  • (_______ precursors pulled ventrally)

• 5. ________ tubes & _______ precursors fuse @ midline

  • (fusing caused by apoptosis of touching walls)

  • Bringing these to midline forms ______ cardiac tube

    • within tube, differentiation of myocardial precursors into ______ fibers begins

• All this is possible because of body folding

• splanchnic, ventrally

  • splanchnic & somatic mesoderm

• splanchnic mesoderm

  • Cardiac crescent cells, myocardial , endocardial

• tubes

• gut tube, Myocardial

• Endocardial, myocardial

  • simple

    • cardiac

• All this is possible because of body folding

Cardiac crescent cells differentiate into myocardial (heart) & endocardial (vessels) precursor cells

Endocardial precursors form endocardial tubes

Simple cardiac tube anatomy

• Heart starts as simple _______

• To become complex organ w separated compartments, tube must contort (left & right atria fold ________; looping)

• tube

• upwards

Heart Looping

• Heart tube continues to grow & bend

  • “Squashes” down on itself

  • Twists to move _____&_____ to correct positions

• Septation occurs as heart loops (______ begin to form)

• while heart is looping, massive ________ also occurring → muscle _______ beginning to form

• left & right ventricles

• walls

• proliferation, walls

Heart Looping

.

Heart formation

• Lateral plate mesoderm → ________ mesoderm

Limb Development

• Lateral plate mesoderm → ________ mesoderm

• splanchnic

• somatic

Limb fields (limb devel)

• ________ from ________ mesoderm undergoes determination to become Limb field (either wing or leg)

  • Undifferentiated site of ________

  • Morphogen involved: possibly _______ family products

    • (morphogen = protein/molecule that serves as the signal during induction)

  • Mesenchyme = 

    • _______ organized mesoderm cells 

    • Derived from ________ mesoderm

    • Gives rise to _____&_____ tissue

  • bilateral at this point; right & left somatic mesoderm begin to form diff limb fields

• Mesenchyme, somatic

  • future limb

  • Hox gene family products

  • Mesenchyme = 

    • Loosely

    • somatic

    • connective & muscle

Limb bud

• 1. Myotome from ______ enter limb fields

• 2. _____+______ contact & push overlying surface ectoderm outward

• 3. Limb bud = Combo of ________+_______+________

• somites

• Mesenchyme + myotome

• mesenchyme + myotome + surface ectoderm

Limb bud

• 1. Myotome from somites enter limb fields

  • Somites ~15‐20 form ______; ~23‐32 form ______

    • Future muscles

  • Morphogens: ______&_______

    • Only specific somites respond to these

• 2. Mesenchyme + myotome contact & push overlying surface ectoderm outward

  • mesenchymal cells from __________ joined by mesenchymal cells from _______ of _______

  • once in respective limb field area, now going to begin differentiation process (rapid division/ proliferation)

  • Buldges result from rapid division / proliferation, pushing against overlying ectoderm

• 3. Limb bud = Combination of mesenchyme + myotome + surface ectoderm

  • Made of rapidly ________ cells; need to stay in contact for limb devel

• wing, leg

• FGF‐8 & FGF‐10

—

• somatic mesoderm, myotome of somites

• dividing

Limb Bud formation

• the most _______ ectoderm cells differentiate & are induced to become ___________ (____)

  • Morphogen: FGF____

    • key activator of ______

  • From here on out, _______ drives bud formation

• (thumb always anterior, pinky posterior)

• AER induces adjacent mesenchyme to differentiate into ________ zone

• ______ form via cell line interactions

• distal, Apical Ectodermal Ridge (AER)

  • FGF‐10

    • AER

  • AER

• (thumb always anterior, pinky posterior)

• Progress

• Axes

Limb Bud formation

• AER induces adjacent mesenchyme to differentiate into Progress zone

  • sends morphogens back towards _________ region. Morphogen: FGF____

• Overall: communication process where diff morphogens get shoved at a tissue, tissue receives morphogen causing differentiation, then uses morphogen (same or diff) to signal back

• Concentration gradient 

  • cells of limb field (mesoderm) closest to ______ undergo most _______ division rates

  • ie cells closest to ________ hear message loudest to start rapid division

• limb field region. FGF‐8

• AER, rapid

• AER

Limb Bud formation

• important morphogens = ______ & ______

  • —> allow establishment of AER & ZPA signaling ceters

• FGF8, FGf10

Limb Development

• Axes via cell line interactions

  • 3 induction intrxns in limb bud generate 3 limb axes

    • informs cells which part of the limb it needs to be

  • 1. P_____-D_____ axis

  • 2. D_____-V_____ axis

  • 3. A_____-P_____ axis 

• 1. Proximal‐distal axis

• 2. Dorsal‐ventral axis

• 3. Anterior‐posterior axis 

Limb Development

• 1. Proximal‐distal axis

  • _______ + _______ zone

• 2. Dorsal‐ventral axis

  • _______ overlying sides of developing limb bud + _______ cells in body of limb bud

• 3. Anterior‐posterior axis 

  • _______ cells @ _______ (posterior margin in base of limb bud) + _______ zone

• AER + Progress zone

• Ectoderm + Mesenchyme

• Mesenchyme ZPA + Progress zone

Limb Devel

• 1. Proximal‐distal axis (AER + Progress zone)

  • ________ = area of mesoderm closest to AER that hears message loudest

  • AER induces _______ cells to proliferate

    • Using morphogens: ______&______

  • PZ cells in close contact w AER continue to proliferate

    

• Progress zone

• progress zone

  • FGF8 & 10

Limb Devel

• 1. Proximal‐distal axis (AER + Progress zone)

  • PZ cells left behind experience ________ concentration fx:

    • Some undergo apoptosis (_______ concentrations = low‐to‐none)

    • Some just slow prolif & come under induction influence from other inducers

  • Effects of other inducers = ______ & ______ expand distally

• morphogen

  • morphogen

• AER & progress zone

Limb Devel

• 1. Proximal‐distal axis (AER + Progress zone)

  • Effects of other inducers = AER & progress zone expand distally 

    • Cells “_______” develop into limb regions & structures

      • 1st ones left behind become _______ 

    • Mechanism still uncertain

• left behind

• proximal

Proximal‐distal axis (limb)

Cells “left behind” develop into limb regions & structures

SZA

SZA

Limb Devel

• 1. Proximal‐distal axis (AER + Progress zone)

  • Disruption/destruction/removal of ______ results in truncation of limb

    • if you shave off layer of ______, limb development comes to grinding halt at that point in development

• AER

• ectoderm

Limb Devel

• 2. Dorsal‐ventral axis

  • (______ overlying sides of developing limb bud + _______ in body of limb bud)

  • Dorsal & ventral patterns give rise to different structures

• (Ectoderm overlying sides of developing limb bud + Mesenchyme cells in body of limb bud)

Limb Devel

• 2. Dorsal‐ventral axis

  • Remember: AER & progress zone expand distally → Cells “left behind” develop into limb regions & structures

  • Along the way…

    • _______ ectoderm sends message “______” 

      • Morphogen: WNT7a

    • _______ ectoderm sends message “______” 

      • Morphogens: BMPs & EN1

      • (bone morphogenic proteins, engrailed1)

• Dorsal “dorsal” 

• Ventral “ventral”

2. Dorsal‐ventral axis

• _______ Morphogen: WNT7a

• _______ Morphogens: BMPs & EN1

dorsal

ventral

Limb Devel

• 3. Anterior‐posterior axis 

  • (Mesenchyme cells @ ZPA + Progress zone)

  • Prior to outgrowth, edge of ______ contacts small group of ________ cells (from _______ mesoderm) in ________ region of early limb bud

  • AER activates these cells, using Morphogen FGF___, to become _______

• AER, mesenchyme, somatic mesoderm, posterior

• FGF‐8, ZPA

Limb Devel

• 3. Anterior‐posterior axis 

  • ZPA characterized by ________ gene activity

    • Releases Morphogen: _______(___)

    • shh ____________ (posterior → anterior) determines digit formation

    • higher shh concentrations induce ________ structures

• sonic hedgehog

• Sonic hedgehog (shh)

• concentration gradient

• posterior

Anterior‐posterior axis (limb)

bank: ZPA, PZ, AER

Extraembryonic membranes (EEM)

• Membranes that develop outside of _______

  • Support embryonic ________

• Develops from _______ & _______ cell lineages

  • Temporarily _______ with embryo

  • Body folds establish boundary btwn _______ & _______ regions

• 4 EEM form during _______ develop

• embryo

  • development

• embryonic & extraembryonic

  • continuous

  • embryo & extraembryonic regions

• vertebrate

Extraembryonic membranes (EEM)

• 4 EEM form during vertebrate develop

  • 1. A______

  • 2. C______

  • 3. A______

  • 4. Y______

• Present to some degree in ALL _______

• _____&_____ fuse after formation to become chorioallantoic membrane (CAM)

• 1. Amnion

• 2. Chorion

• 3. Allantois

• 4. Yolk sac

—

• vertebrates

• Chorion & Allantois

EEM Formation

• Derived from ____ germ layers (mesoderm/endoderm/ectoderm), extends out of _______

• Somatopleure 

  • fusion of __________ + ______derm

• Splanchnopleure 

  • fusion of __________ + ______derm

• 3, embryo

• Somatic mesoderm + Ectoderm

• Splanchnic mesoderm + Endoderm

EEM Formation

EEM Formation – MAMMALS

• Mammals have same 4 EEM

  • 1)A______ 2)C______ 3)A______ 4)Y______

• _____&_____ 1st fuse to become _______ (CAM)

• Then, (in mammals) fuse w maternal endometrium to become ________

• 1)Amnion 2)Chorion 3)Allantois 4)Yolk sac

• Chorion & Allantois 1st fuse to become chorioallantoic membrane (CAM)

• placenta

EEM Summary

• Amnion & Chorion originate from _________

• Allantois & Yolk sac originate from _________

—

• _______ = hydration; protection 

• _______ = no function until fusion with chorion

• _______ = nourishment

• _______ = respiration

• Somatopleure

• Splanchnopleure

—

• amnion

• allantois

• yolk sac

• chorion

EEM Summary

• Fused Chorion + Allantois

  • Birds (chorioallantoic membrane – CAM)

    • Origin: _____+_____

    • Function: _____+_____ management

  • Mammals

    • ________ forms from splanchnic mesoderm + trophectoderm

      • Fuses w ______, then maternal _______, to become placenta

• Splanchnopleure + Somatopleure

• respiration + waste management

• Chorion, allantois, endometrium

• Growth that occurs when cells increase in size = __________

• Growth that occurs when cells increase in number = __________

(Can occur in combination or separately)

• Hypertrophy

• Hyperplasia

• Neural progenitor = Produces ______ AND _______ cells; _____‐potent

• ________ = generic term for ANY neuronal process

• ________ = bundles of axons from a ganglion

• ________ = Terminally post‐mitotic cell of nervous system capable of receiving & transmitting information via electric impulses

• ________ = group of neuronal soma in the ____NS

  • Sensory or Autonomic

• Basal lamina/Basement membrane

  • Extracellular matrix that attaches, anchors, & surrounds almost all epithelial tissues & structures in the body

• neurons & glial cells; multipotent

• Neurite

• Nerve

• Neuron

• Ganglion, PNS

• Basal lamina/Basement membrane

  • Extracellular matrix that attaches, anchors, and surrounds almost all epithelial tissues and structures in the body

Nervous tissue growth & devel 

• Review: Brain development

  • Neural tube constricts & _______ via _______

  • ⇒ Regional _____& _____

  • Progresses from 3‐part brain → 5‐part brain

• End of neurulation = Fully formed _______

• thickens, cell division

• differentiation & proliferation

• neural tube

End of neurulation = Fully formed neural tube

• Cells produced proteins that coated outer surface of neural tube

  • = ________

• Neural tube consists of _______ layer of multipotent ___polar neural ________

  • ___polar – 1 process extending from each end of soma

    • 1 process extends towards ______ (future _______)

    • Other process extends away from cavity toward ______ of neural tube (_______)

  • ______ MIGRATES back & forth between ventricular & outer surfaces

• Basal lamina

• SINGLE, bipolar, progenitors

  • Bipolar

    • cavity (ventricle)

    • outer surface (basal lamina)

  • Soma

• neural tube wall

• epiblast ectoderm

• part of neural tube up against ventricle

• ventricular zone

• basal lamina

Neurogenesis = making neurons

• While migrating, neural progenitors _________

• Division occurs only when soma are near _______ surface (_______ zone)

  • (divison = physical separation / cytokinesis / splitting & production of 2 daught cells)

• Near _______ surface, cells enter rest phase of mitosis (_______ zone)

  

• proliferate

• ventricular surface, ventricular zone

• outer surface, Marginal zone

Neurogenesis 

• Due to combination of ______ soma and massive _______, neural tube cells take on _______ appearance

  • BUT still are only a single layer (_______)

    

• migrating, proliferation, stratified

  • Pseudostratified

Neurogenesis - 2 phases

• 1. ________

  • Symmetric division only

• 2. ________

  • Symmetric + Asymmetric division

• 1. Expansion

• 2. Neurogenic

Neurogenesis 

• 1. Expansion

  • Symmetric division only (2 identical daught)

  • Prelude to true _______

  • Neural tube ________ (remember brain region formation?)

• neurogenesis

• thickening

Neurogenesis 

• 2. Neurogenic

  • Symmetric + Asymmetric division

  • aka __________

  • Asymmetric division ⇉ 1 _______ + 1 _______ neuron

    • (_____ neuron = neuron PRECURSOR); can still prod daught cells

• True neurogenesis

• 1 progenitor + 1 transiently amplifying (TA) neuron

Neurogenesis 

• Division outcomes as progenitor’s DNA ages:

  1. Expansion

     • Symmetric division → 2 identical ________

     • ______s can return to the beginning to continue cycle 

  2. Neurogenic

     • Asymmetric division → progenitor cell splits into 1 progenitor cell + 1 ________ (TA / Terminally post‐mitotic)

     • _______ can keep dividing to continue cycle

• neural progenitors

• NPs

—

• TA neuron

• Progenitor

Neurogenesis 

• Neurogenic phase

  • Progenitor can keep dividing to continue cycle

    • symmetric divis → 2 identical _______

    • Asymmetric divis → 1 _______ + 1 _______ cell

    • Symmetric divis (last stage) → 2 _______ cells 

      • (______ first; then astrocytes)

• 2 TA neurons

• TA neuron + glial cell

• 2 glial cells 

  • (Oligodendrocytes first; then astrocytes)

Neurogenesis

Neurogenic phase

• Asymmetric division

  • 1 daughter cell not _____polar

  • Wraps around ______ zone process of ________ cell & “climb” toward _______ zone

• bipolar

• marginal zone, progenitor, marginal

Neurogenic phase (neurogenesis)

• Neural tube changes

  • Along tube, regional difference in _______ rates & types of _______

    • Produce distinct regions of __NS in specific anterior‐posterior pattern

  • _______ begin to differentiate & become post‐______ as leave _______ zone (lose ability to divide) 

    • As things get more crowded, newer cohorts of _______ must migrate further out 

    • Forms ______ of cortex (no longer _________)

      • most recently produced ones at _______ layer

• cell division rates, daughter cells

  • CNS

• Neurons, post‐mitotic, intermediate zone

  • neurons

  • layers of cortex, pseudo-stratified

    • outermost

Post‐natal neurogenesis

• Rare in ENDOtherms (warm blooded)

• General mammalian pattern: 

  • ______ evidence of ______ beyond sexual maturity

  • In adults, typically restricted to _____campus, sub______ zone of lateral ventricle w migration to olfactory ______

  • Exceptions….

• Rare

• General mammalian pattern: 

  • Little, neurogenesis

  • hippocampus, subventricular, bulb

Post‐natal neurogenesis

• Exceptions (to general mammalian pattern):

  • _______ that engage in seasonal, dramatic changes in behavior

    • Neurogenesis in ________ related to:

      • Song acquisition & performance

      • Migration

      • Caching (storing & successfully retrieving stored food items)

  • ______ during olfactory memory formation

    • Neurogenesis in forebrain w migration to _______ (late as 4 wks)

    • Neurogenesis in ________ possible throughout life

• Birds

• hippocampus

—

• rodents

• olfactory bulb

• hippocampus

• Most post‐natal _________ growth = result of “growth” of neurites, especially ________

• Nervous tissue growth postnatally occurs largely thru ______ (incrs size)

• nervous tissue, axons

• hypertrophy

Axon initiation

• ______ of ______ neuron adjacent to basal lamina = signaled to become _______

• As layers form in neural tube, _______ signal _______ to exit neural tube

• Neurite, post‐mitotic neuron, axon

• morphogens, axon

Axon growth cone = how processes grow

• Tip of axon differentiates into _______ growth cone (free from soma)

• Cytoplasmic “suitcase” – _______ loaded w everything needed for _______ synthesis

  • Cytoplasmic proteins (ribosomes, mRNA)

  • Actin molecules

  • Microtubules

• Enables ________ survival, elongation, & ________ proteins

• Emancipates growth cone from having to wait for ______ to travel from ______

• _______ of growth constantly pull & cause axon to elongate (fingers reaching out for target)

• autonomous

• growth cone, protein

• axon, navigation

• proteins, from soma

• Filopodia

Axon growth cone behavior = dependent on which signals the ______ encounter

• ______/adhesion molecs → “_______”

  • Ex. Cell Adhesion Molecs (CAMs)

• ________ molecs → “______”

• Physical/mechanical ________ → “_______”

  • Stiff cells (eg. w collagen)

filopodia

• Attractant/adhesion → “Advance”

• Repellent → “Retreat”

• barriers → “Go around”

Pioneer axons

• 1st axons to exit _______ / grow into a ________

• have _______ growth cones; very _______ acting

• Follow _______ signals & forge _______ to correct _______

• Produce ______‐specific _______ & incorporate into ________ along way

  • Attract & guide _______ axons

    • Ex. In PNS, from neurons in the same ganglia as the pioneer axon

  • Cause ______ axons to ______

• neural tube, new region

• Hyperactive, fast

• regional, pathway, target tissue

• region‐specific CAMs, axon membrane

  • follower

  • follower, adhere

Growing axon behavior

• 1. Following ______ signals, growing axon advances to _______ target 

  • Once shared _____ detected, growth cone pulls axon in that direction

• 2. Reach _______ target

• 3. Signals that attracted to _______ target become _____/non‐______ after leaving _______ target

  • depending on where axon is relative to _______ target, function of same molecule can switch between ______/______

• 4. At _______ target: _______ branches & each branch differentiates into ________

• attractant, intermediate 

  • CAM

• intermediate

• intermediate, repulsive/non‐attracting, intermediate

  • intermed target, attractant / repulsive 

• Final target, Growth cone, synapse

Where do PNS neurons come from?

• Remember neural tube formation:

  • Primordial ______ comes from _____derm

  • Formation of tube via invagination

    • 1. Notochord induces epiblast _______ ↠ _______ cells

    • 2. Bending of neural ______ into neural _____

    • 3. Closure/pinching off of neural ______ into neural tube

loose ends = Neural crest cells

• CNS, ectoderm

• Formation via invagination

  • ectoderm , neural plate cells

  • plate, groove

  • groove

PNS neurons come from Neural crest cells (NCCs)

• Epiblast cells at _______ of closing ________ undergo determination → Future ________ cells

• Become ______‐like, _____potent cells that ______ thruout body in well‐defined patterns

  • Capable of differentiating into either _______ or _______

  • Not fully pluripotent bc they cant differentiate into _______

• margins, neural tube, neural crest

• pluripotent‐like, multipotent, migrate

  • mesoderm or ectoderm

  • endoderm

Neural crest cells (NCCs)

• Capable of differentiating into either mesoderm or ectoderm

• Mesodermal cells → ________ (cells of mesoderm) differentiate into _____&______ tissues

  • Smooth muscle, Osteoblasts /clasts, Adipocytes, chondrocytes

• Ectodermal cells → cells of _______

  • Melanocytes

  • Schwann cells 

  • Neurons

• mesenchyme, connective & muscle

• PNS

Growth of PNS

• Just like neurons of CNS, PNS neurons rely on ________ activity

• Start w ________

• Ea ______ axon then produces ______‐specific ______ that attract, guide, & adhere subsequent ________

• Single ______ → form ______ bundles → which form ______ → which form ______

• growth cone

• pioneer axons

• follower, region‐specific CAMs, follower axons

• Single axons → Axon bundle → Fascicle → Nerve

PNS ________ = held together by layers of connective tissue

• endo /peri /epi neurium

axon bundles

PNS axon bundles = held together by layers of connective tissue

• ENDOneurium

  • Wraps around a single neuron’s ______, its associated ______ cells & _______

• PERIneurium

  • Wraps around bundles of _______-wrapped _______, ________, & ________ tissue

  • Forms a ______

• EPIneurium

  • Wraps around bundles of _______, ________, & ______ tissue

  • Forms a ______

• axon, glial cells, capillaries

• axons (endoneurium wrapped), blood vessels, adipose tiss

  • fascicle

• fascicles, blood vessels, adipose tissue

  • nerve

PNS axon bundles – held together by layers of connective tissue

• Endoneurium, Perineurium, Epineurium

Once axons synapsed:

• Functional verification = _______

• An axon will _______ its connections

  • Send out new ________ w/in target area

  • Allow existing ______ to _______

• Response to activity between _____&_____

  • “Use it or lose it.”

  • “Use it a lot, recruit more.”

• Response to _______ of organism

  • As organism grows, _______ to _______ will change

  • Axon ________ as body grows

    • Axon growth shifts to ________ (growth between 2 landmarks) 

    • No longer ________ driven (not growing from ________ anymore; axon gets ________ as it’s lengthened)

Axon grwth b4 synapsing: growth cone

After synapsing: interstitial growth

• Fine tuning

• shift

  • new branches

  • branches, regress

• axon & target

• growth of organism

  • physical distance, ganglia

  • lengthens

    • interstitial

    • growth cone (end of axon; stretched out)

Axon grwth b4 synapsing: growth cone

After synapsing: interstitial growth

Dendrites

• Less is known, ______ are more murky

• Dendrites have their own _______

  • Appear as mini _______

• Dendrite _______ behavior can be variable

  • Sometimes responds opposite to ______ growth cone

  • Sometimes responds ______ (when synapsing w axon is required)

• dendrites grow throughout life

• morphogens

• growth cones, growth cones

• growth cone

  • axon, identically

Dendrites

• Complexity of _______ = dependent on amount of incoming ________

  • Multi‐dendrite vs simple dendrite

  • Innervation activity levels affect dendritic complexity

• Dendrites = VERY dynamic

  • Ex. In mice, some dendrites in visual system can appear & disappear within minutes when exposed to stimuli

• branching, innervation

Myelin

• Both _______ & _______ produce myelin sheaths around some axons

  • 1 ______ makes multiple sheaths, 1 ______ makes 1 sheath

• _______ (CNS);      _________ (PNS)

  • myelin appears as white matter of _______

    • ______ matter = Not myelinated (e.g., soma, dendrites, etc)

• Enables fast _______ conductance along _______

  • is an electrical _______

  • Accelerates conductance by localizing ______ channels at ________ (short gaps btwn adjacent myelin sheaths)

• Myelination = dynamic throughout life

  • ______ myelin plasticity different from _______ myelin plasticity

• oligodendrocytes & schwann cells

  • oligo, schwann

• Oligo = CNS, Schwann = PNS

  • CNS; Gray

• electrical, axons

  • insulator

  • Na+, Nodes of Ranvier

• CNS, PNS

CNS: Oligogenesis

• In rodents: ____________ cells (OPCs) can…

  • ...undergo ______ to produce more _______

  • AND/OR

  • ...differentiate into a post‐______ pre‐_______ oligodendrocyte (PO)

    • ~80% PO attrition rate (fail to ______) 

    • Remaining ~20% of POs migrate to ______ & become _______, producing myelin

CNS myelin plasticity

• _______ occurs throughout life

  • In human adults, ______ still active

  • Numbers peak during _______ age

• Oligodendrocyte precursor

  • division, oligodendrocytes

  • post‐mitotic pre‐myelinating oligodendrocyte

    • survive

    • axon, oligodendrocytes

• Oligogenesis

  • OPCs

  • middle age

PNS: Schwann cell (SC) classes

• Myelinating SC

  • Produce ______ & wrap ______ in _______

  • Nourish axons

• Remak SC

  • __________

  • Nourish axons

• myelin sheaths, axons, myelin sheaths

—

• Non‐myelinating

PNS: Schwann cell development

• ________ ↠ Schwann cell precursors (SCP)

• SCPs _______ & bounded by associated _______

  • Once associated w ______, SCPs become dependent on _____ for _______

• SCPs stop migrating:

  • now classified as _______ (___)

  • _______ still growing

  • figure out which axons to myelinate via _______ sorting

    • Based on _______ of axon

      • Big diameter (thick) = ______

      • Small diameter (thin) = ______

  • Become “self‐supporting” & mature into myelinating Schwann cells

• NCCs

• migrate, axons

  • axon, axon, survival

• Immature Schwann cells (ISC)

  • Axon

  • Radial sorting

    • diameter

      • Big = Myelin

      • Small = No

  • Become “self‐supporting” & mature into myelinating Schwann cells

PNS myelin plasticity: Response to injury

• _______ nerves can undergo _______

• PNS ________ possible through _______ plasticity (specifically _______ SCs)

  • Caveats:

    • 1. Effective only on _________

      • Regeneration rate too ______ to completely heal traumatic nerve damage

    • 2. SCs competence ______ with _______

• Peripheral, regeneration

• regeneration, Schwann cell (remak SCs)

  • minor injuries

    • slow

  • diminishes w/ age

SC-mediated PNS regeneration

• 1. Peripheral nerve injury

• 2. Both ______&______ SCs undergo _________

  • _________ de‐myelinate

  • & both convert into _______ SCs

• 3. Newly programmed _______ SCs & ________ break down _______ part of axon

  • = Wallerian degeneration*

  • * occurs to lesser extent & mechanism less understood in CNS

• 4. _______ SCs clear out ________ tissue

  • Produce _______ factors to ________ re‐growing axon

• 5. ______ SCs form scaffold to guide re‐growing _______ back to ______

• 6. _______ proliferate; reprogram to turn on ________ genes (promote axonal growth)

• 7. Newly re‐programmed ________ SCs then re‐myelinate axon

• Myelinating & Remak, reprogramming

  • Myelinating SCs

  • Repair SCs

• Repair, macrophages, damaged

  • = Wallerian degeneration*

• Repair, damaged

  • trophic factors, nourish

• Repair, axon, target

• Repair SCs, myelinating

• myelinating