How to get a head in life: The development of the craniofacial complex

Rich Schneider, PhD

Department of Orthopaedic Surgery

University of California San Francisco

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Modified from Yokochi, Rohen, and Weinreb (1989)

Identify molecular and cellular mechanisms

that control head development

and enable structural integration

How do craniofacial precursor cells

learn where and when

to differentiate into appropriately

patterned components of the head?

Provide data necessary to induce repair

and regeneration of tissues affected by

birth defects, disease, and trauma

bird egg

Hamburger and Hamilton (HH) Staging System for Birds

HH9.5

Modified from Larsen (1993)

neural crest

endoderm

non-neural ectoderm

neural ectoderm

mesoderm

Modified from D. Noden

HH8+ HH9 HH9+ HH9.5 HH10 HH11

Kulesa and Fraser, Development (2000)

bird (chick) mammal (mouse)

chick retrovirus (SNV-lacZ)

Evans and Noden (2006) Jiang et al. (2002)

transgenic mouse (Wnt1-Cre/R26R)

bird (chick) mammal (mouse)

neural crestskeletal tissues (bone and cartilage, dentin)

neural tissues (neurons, sensory ganglia, glia)

connective tissues (dermis, fat)

vascular tissues (pericytes, smooth muscles)

non-neural ectoderm

epidermal tissues (nails, hair, feathers, beaks)

mesodermskeletal tissues (bone and cartilage of skull)

connective tissues (dermis, fat)

muscular tissues (voluntary muscles)

vascular & hemato tissues (vessels, osteoclasts)

neural ectoderm

neural tissues (brain, motor nerves, retina)

endoderm pharyngeal tissues (auditory tube, pouches)

glandular tissues (thyroid, thymus, parathyroids)

HH 8

HH 12

HH 17

neural crestnon-neural ectoderm

placodal neurons

mesoderm

muscle plate

HH 10

endoderm

neural ectoderm

notochord

Modified from D. Noden

neural crest

non-neural ectoderm

mesoderm

neural ectoderm

endoderm

What are the hierarchical levels of organization and critical interactions that control

craniofacial development?

non-neural ectoderm

musculature

vasculature

osteoclasts

skeleton

connective

tissues

epidermal appendages

nerve

ganglia

mesodermneural crest

What are the hierarchical levels of organization and critical interactions that control

craniofacial development?

non-neural ectoderm

transplantation

skeleton

connective

tissues

epidermal appendages

nerve

ganglia

musculature

vasculature

osteoclasts

...genes...cells...tissues...organs...systems...

mesodermneural crest

What are the hierarchical levels of organization and critical interactions that control

craniofacial development?

non-neural ectoderm

transplantation

skeleton

connective

tissues

epidermal appendages

nerve

ganglia

musculature

vasculature

osteoclasts

...genes...cells...tissues...organs...systems...

mesodermneural crest

What are the hierarchical levels of organization and critical interactions that control

craniofacial development?

HH37

quail

Schneider et al. (2001)

chick

Schneider (1999, 2005)

HH37 HH25 HH9.5

quail

Schneider et al. (2001)

fn

mx

ma

chick

Schneider (1999, 2005)

duck

exploit differences:

size

shape

pattern

growth rate

quail

1cm

Tokita and Schneider, Developmental Biology (2009)

duckquail

1cm

Tokita and Schneider, Developmental Biology (2009)

duckquail

1cm

Tokita and Schneider, Developmental Biology (2009)

HH37 HH25 HH9.5

quail

duck

HH9.5quail duck

500µm

Fish et al., Development (2014)HH9.5

quail duck

Quail–duck chimeric transplant system

bilateraltransplant

200µm

quail

duck

HH36

2mm

Q¢PN

forebrain

future jaw region

Quail–duck chimeric transplant system

eye

HH21

duck

HH36

quail

duck

2mm

Schneider and Helms, Science (2003)

Q¢PN

forebrain

future jaw region

Quail–duck chimeric transplant system

eye

HH21

duck

HH36

quck

duck

2mm

Schneider and Helms, Science (2003)

Q¢PN

HH42

duail

Quail hosts develop duck-like upper bills host after receiving duck neural crest cells

Schneider and Helms, Science (2003)

duck(host)

quail(donor)

quck(chimera)

eye

Q¢PN

HH37

Both quail donor and duck host-derived tissues are patterned by neural crest mesenchyme

egg tooth

Schneider and Helms, Science (2003)

qumu

emu host = HH27quail donor = HH34

Hall et al., Developmental Biology (2014)

Quail and duck have distinct embryonic feather bud patterns

quail

duck

HH34 HH35 HH36

Eames and Schneider, Development (2005)

short bud

HH36

condensation

placode

dense dermis

HH34

epidermis (host)

dermis (donor)

HH33

Cellular program for feather development

follows a distinct timetable

long bud

HH37

Eames and Schneider, Development (2005)

Unilateral transplants provide an internal control

donorhost

HH33

2mm

HH37

200µm

quck

HH9.5

quail duck

unilateraltransplant

Eames and Schneider, Development (2005)

Unilateral transplants provide an internal control

donorhost

HH33

2mm

HH37

Eames and Schneider (2005)

200µm

quck

HH9.5

quail duck

unilateraltransplant

2mm2mm22mm2mm2mm2mmmm2mm2mm2mm2mm2mm2mm2mm2mm2mm

HH337

EamesEamesEamesEamesEamesEameEamesEamEameEamesEamEameEamesEamesEamesEaEameEameEEaE and and and dand nd S hSchneSchneSchneSchnechnSchneSchneSchnSchneSchnehnhneneiider ider iderideriderider iderideriderideidererderiderideriderideriderder ((2005(2005(2005(2005(2005(2000(20(20000000000 ))))))))))

HH37

Eames and Schneider, Development (2005)

Unilateral transplants provide an internal control

200µm

HH9.5

quail duck

unilateraltransplant

2mm

adult

1cm

quail duck

500µmQ¢PN

donorhost

Eames and Schneider, Development (2008)

HH29

quck

donorhost

quck

HH37

2mm

donorhost

quck

HH37

2mm

quailduck

2mm

HH40HH37

Eames and Schneider, Development (2008)

duckHH25

2mm

donorhostquckHH25

quailHH28

Q¢PN

ColII

col2

HBQ

200µm

Eames and Schneider, Development (2008)

Q¢PN

BrdU

Alk Phos duck

quck

Precocious transition to differentiation

Hall et al. (2014)

HH26

HH26

HH24

HH24

quckduck quail

2mm

HH33 HH34host donor

HH31

HH34 HH37HH34

HH36 HH39HH36

Anatomy of the jaw joint differs between duck and quail

quailduck

HH38

Solem et al., Developmental Biology (2011)

Species-specific morphology of the jaw adductor complex

quailduck

HH38

Solem et al., Developmental Biology (2011)

myf5

quck

Q¢PN

Tokita and Schneider, Developmental Biology (2009)

quckduckquail duckquail

HH33HH33 HH36HH36HH33

R

C

Tokita and Schneider, Developmental Biology (2009)

Neural crest patterns and integrates the craniofacial complex during

development and evolution

neural crest

neural crest

Neural crest patterns and integrates the craniofacial complex during

development and evolution

Disruptions to neural crest during patterning and integration can cause abnormal development

of the craniofacial complex

From Dr. K. Vargervik

UCSFKristin Butcher

Camille Curantz

Erin Ealba

Brian EamesJennifer Fish

Stephanie Gline

Jane Hall

Andrew JheonAmy Merrill

Christian Mitgutsch

David Sitbon

Christian SolemRachel Sklar

Johanna Staudinger

Zuzana Szolgayová

Masayoshi TokitaKate Woronowicz

RIKEN CDBRaj Ladher

Suzanne Mak

FUNDINGACKNOWLEDGMENTS