Thesis defense talk KyungHwa (Kirsten) Lee 2009

Sex differences in a C. elegans sensory behavior

Kyung Hwa LeeAdvisor: Douglas S. Portman

Interdepartmental Graduate Program in Neuroscience

Sex differences in the neural circuitry and behavior

Swaab et al., 2003

Females

Anorexia nervosaAnxiety disorder

Unipolar depression

Males

AutismADHD

Schizophrenia

Gender influences neurological and mental health

SEX Sex differencesin common behaviors

and/or

structure

(e.g., neuronal number, connectivity)

molecular, cellular properties in the same neural circuit

(e.g., neurochemical composition)

Sex differences in the neural circuitry

Sex differences can arise independently of sex hormones

Agate et al., 2003

♀♂


Agate et al., 2003

♀♂HVC HVC

♂ ♀


Agate et al., 2003

♀♂

Sex chromosome in the brain itself(i.e., cell-intrinsic sex determination)contributes to neural sex differences

HVC HVC

♂ ♀

Sex differencesin behaviors

Sex chromosomes

Does “Neural sex” control the sex of neural circuit and behavior?

Sex differences in the neural circuitry

C. elegans as a model system to study sex differences in the neural circuit and behavior

• the complete wiring diagram of the Hermaphrodite neural circuitry

• no sex hormones

• well-defined cell-intrinsic sex determination pathway

• easily tractable, relatively simple behaviors

• available tools to tweak the neural function at the single neural level

XX Hermaphrodite

959 somatic cells

X0 Male

1031 somatic cells

somaticgonad

tail tip

Vulva

Oocytes Sperm

SpermMale tail sensilla

Portman, 2007

C. elegans exhibits extensive sex differences

Cell-intrinsic sex determination pathway regulates all known somatic sex differences in C. elegans

Sex chromosome

XX

X0

⚥

♂

tra-1

tra-1

Terminal sex regulator


• XX animals carrying tra-1 null mutation develop as complete normal somatic XX males (Hodgkin, 1987; Hodgkin and Brenner, 1977)

Sex chromosome

XX

X0

⚥

♂

tra-1

tra-1



• XX animals carrying tra-1 null mutation develop as complete normal somatic XX males (Hodgkin, 1987; Hodgkin and Brenner, 1977)

• Cell-autonomous control of sex differentiation by TRA-1 (Hunter and Wood, 1990)

Sex chromosome

XX

X0

⚥

♂

tra-1

tra-1


HermaphroditeTotal 302 neurons

MaleTotal 383 neurons

Sex differences in the C. elegans nervous system

8 Hermaphrodite-specific neurons

VC HSN

89 Male-specific neurons

CEM CA/CPRn, HO, SP, PC

EF, DV, DX, PDC, PGA, PV

(mate searching, mating)

(egg-laying)

Portman, 2007

HermaphroditeTotal 302 neurons

MaleTotal 383 neurons

Sex differences in the C. elegans nervous system

“Core”294 neurons

feedingsmell, taste

touchmovement

8 Hermaphrodite-specific neurons

VC HSN

89 Male-specific neurons

CEM CA/CPRn, HO, SP, PC

EF, DV, DX, PDC, PGA, PV

(mate searching, mating)

(egg-laying)

Portman, 2007

Sex differences in the core nervous system at the molecular level

Male

srj-54::YFP

AIM

AIM

Hermaphrodite

srd-1::GFP

ASI

ADF

ASI

Troemel et al.,1995

ADF

Portman DS, unpublished

Sex differences in common behaviors

core neural circuitryfeeding

smell, tastetouch

movement Male. olfaction

Herm. olfaction

e.g.

e.g.

?

Do common behaviors differ between sexes?

Olfaction is mediated by core neural circuitry

olfactory neuronal circuit Sensory neurons

Benzaldehyde (bz) 2-‐Butanone (bu)

Diacetyl (da) Pyrazine (py) Repellents

AWC AWA AWB

InterneuronsAIY AIZ

RIA





AWC AWA AWB

Motor neurons

SMD RMD

InterneuronsAIY AIZ

RIA





AWC AWA AWB

control B A odorant

CI = (A-B) / total

Are there sex differences in C. elegans olfaction?

Bargmann et al., Cell (1993)

Sex differences in C. elegans olfactionCh

emot

axis

Inde

x

Odorant dilution

diacetyl(AWA)

pyrazine(AWA)

benzaldehyde(AWC)

2-butanone(AWC)

10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$0

1

0.5

0

1

0.5

* ***

***

* * ***

*

Hermaphrodite Male

Lee and Portman (2007) Curr. Biol.

Sex differences in C. elegans olfactionCh

emot

axis

Inde

x

Odorant dilution

diacetyl(AWA)

pyrazine(AWA)

benzaldehyde(AWC)

2-butanone(AWC)

10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$0

1

0.5

0

1

0.5

* ***

***

* * ***

*

Hermaphrodite Male

Males are also attracted to 4 canonical odorants

Male olfaction is significantly reduced in response to da, bz

Lee and Portman (2007) Curr. Biol.

Olfactory preference assay

worms

Odorant B+ NaN!

Odorant A+ NaN!

Lee and Portman (2007)


worms

Odorant B+ NaN!

Odorant A+ NaN!

OPI =b – a

b + a


a b


worms

Odorant B+ NaN!

Odorant A+ NaN!

OPI =b – a

b + a


worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

a b


worms

Odorant B+ NaN!

Odorant A+ NaN!

OPI =b – a

b + a


worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

worms

Odorant B+ NaN!

Odorant A+ NaN!

a b

Hermaphrodite MaleOPI

–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

daAWA

pyAWA

bzAWC

bzAWC

Odorant

AOdorant

B

Two sensory neurons


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

daAWA

buAWC

pyAWA

iaaAWC

Single sensory neuron


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

Each sex has distinct and characteristic olfactory preferences


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC



–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

daAWA

pyAWA

bzAWC

bzAWC

Odorant

AOdorant

B

Two sensory neurons


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

daAWA

buAWC

pyAWA

iaaAWC



–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC



–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

daAWA

pyAWA

bzAWC

bzAWC

Odorant

AOdorant

B

Two sensory neurons


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC

daAWA

buAWC

pyAWA

iaaAWC



–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


–1 +10

A B

py / bz***

da / py***

da / bz***

*bu / bz

AWA

ODORANT

AWC

AWA AWC

AWA AWA

AWC AWC


Does gonad influence?

Do sex-specific neurons contribute to?

How does sexually different olfaction arise?

Gonadal signaling is not necessary for sex difference in olfaction


L1 L2 L3 L4Embryo

Herm.-specificcircuitry

Male-specificcircuitry

Mating

Egg laying

Mate searching

The C. elegans life cycle

Adult

Sexual differences in olfaction precede sex-specific differentiation

The core nervous system itself may regulate sexually different olfaction

Sexual differences in olfaction precede sex-specific differentiation

core neural circuitry

Sex differences in olfactory behaviors

?orXX X0

molecular, cellular properties in the same neural circuit

Does “Neural sex” generate sexually different olfactory behaviors?

Sex chromosome

XX

X0

⚥♂

tra-1

tra-1


The terminal sex regulator, tra-1, controls sex difference in olfactory preference


Sex chromosome

XX

X0

⚥♂

tra-1

tra-1


Hermaphrodite Male XX Pseudomale

da py

bzpy

Wild type

tra-1

Wild type

tra-1

A

OPI–1 +10

AWA AWA

OPI–1 +10

B da py

***

AWA AWC

Wild type

AWA AWA

Prab-3::fem-3(+)

oxEx862oxEx863

Posm-5::fem-3(+)

fsEx160fsEx161

Pglr-1::fem-3(+)

fsEx158fsEx159

******

******

*

Hermaphrodite Male XX Pseudomale

da py

bzpy

Wild type

tra-1

Wild type

tra-1

A

OPI–1 +10

AWA AWA

OPI–1 +10

B da py

***

AWA AWC

Wild type

AWA AWA

Prab-3::fem-3(+)

oxEx862oxEx863

Posm-5::fem-3(+)

fsEx160fsEx161

Pglr-1::fem-3(+)

fsEx158fsEx159

******

******

*

The terminal sex regulator, tra-1, controls sex difference in olfactory preference


⚥

♂

tra-2 tra-1XX

X0

fem-3

tra-2 tra-1fem-3

Reprogramming the sex of the core neural circuit

Prab-3::fem-3(+)

Wild type Sexual mosaics

⚥

♂

tra-2 tra-1XX

X0

fem-3

tra-2 tra-1fem-3

Reprogramming the sex of the core neural circuit

Prab-3::tra-2(ic)

Prab-3::fem-3(+)

Wild type Sexual mosaics


Neural sex-transformation was successful!

Prab-3::fem-3(+)Hermaphrodite

Wild typeHermaphrodite

Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E



Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E

DIC

srj-54::GFP

Male Herm.





Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E



Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E



Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E

Masculinizednervous system

DIC

srj-54::GFP

Male Herm.

Sex transformation of core neurons at the level of sex-specific gene expression





Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E



Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E



Wild typeMale

DIC

tph-1::GFP(Midbody)

pkd-2::GFP(Head)

srj-54::GFP(Head)

pkd-2::GFP(Tail)

A

B

C

D

E

Masculinizednervous system

DIC

srj-54::GFP

Male Herm.

Neurons masculinized

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

None

Prab-3::fem-3(+)All

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

******

WT

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA


Neural sex determines the sex phenotype of olfactory preference


Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

None

Prab-3::fem-3(+)All

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

******

WT

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA


Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

Olfactory Preference Index (OPI)

HermaphroditeMale

–1 +10

da py

***

wild type

Prab-3::tra-2(ic) #4

Prab-3::tra-2(ic) #8***

***

Neurons feminized

None

All

WT

Prab-3::tra-2(ic)


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

WTPrab-3::tra-2(ic)

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

***

***None

All

Neural sex determines the sex phenotype of olfactory preference

Sex-transformation of subsets of core neurons

Sensory neurons

Interneurons


Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

None

Prab-3::fem-3(+)All

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

******

Posm-5::fem-3(+)SensoryNeurons

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

******

WT

Pglr-1::fem-3(+)Interneurons

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA Hermaphrodite Male

OPI–1 +10

da pyAWA AWA


Neural sex modification on sensory neurons generate sexually different olfaction

Neurons feminized

None

Sensory neurons

None


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

***

Posm-5::tra-2(ic)

Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

*** Posm-5::tra-2(ic)

WT

WT

Sensory neurons


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***

***


HermaphroditeMale

–1 +10

da py

***

wild type


Prab-3::tra-2(ic) #8***

***

Sexually different properties of the sensory neuronscontrol the sex phenotype of olfactory preference

AWA

AIY AIZ

RIA

AWC AWB

SMD RMD

Sex-transformation of a single pair of sensory neuron

AWA

AIY AIZ

RIA

AWC AWA AWB

SMD RMD

Sex-transformation of a single pair of sensory neuron

AWA Podr-7::fem-3(+)

**

***

None

Hermaphrodite Male

OPI–1 +10


OPI–1 +10

da pyAWA AWA

WT


Single sensory neurons impart sex difference to olfactory preference behavior


**

***

None

Hermaphrodite Male

OPI–1 +10


OPI–1 +10

da pyAWA AWA

WT


Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

Podr-7::tra-2(ic)

None

AWA*

**

WT

Neurons feminized



**

***

None

Hermaphrodite Male

OPI–1 +10


OPI–1 +10

da pyAWA AWA

WT


Hermaphrodite Male

OPI–1 +10

da pyAWA AWA

Podr-7::tra-2(ic)

None

AWA*

**

WT

Neurons feminized

AWA neurons are sexually differentiated at the molecular levelto adopt sex differences in olfactory preference


AWA neural sex regulates olfactory circuit function

AWA

AIY AIZ

RIA

AWC AWB

SMD RMD

X0

Male Olfaction

AIY AIZ

RIA

AWC AWA AWB

SMD RMD

XX

Herm. Olfaction

Chem

otax

is In

dex

Odorant dilution

diacetyl(AWA)

pyrazine(AWA)

benzaldehyde(AWC)

2-butanone(AWC)

10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$0

1

0.5

0

1

0.5

* ***

***

* * ***

*

Hermaphrodite Male


How AWA neurons are sexually different?

AWA

Herm. Male

AWA

Da Da

?

Py Py

Chem

otax

is In

dex

Odorant dilution

diacetyl(AWA)

pyrazine(AWA)

benzaldehyde(AWC)

2-butanone(AWC)

10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$0

1

0.5

0

1

0.5

* ***

***

* * ***

*

Hermaphrodite Male



AWA

Herm. Male

AWA

Da Da

?

Py Py

Chem

otax

is In

dex

Odorant dilution

diacetyl(AWA)

pyrazine(AWA)

benzaldehyde(AWC)

2-butanone(AWC)

10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$0

1

0.5

0

1

0.5

* ***

***

* * ***

*

Hermaphrodite Male



XXX

odr-‐7

AWA

Herm. Male

AWA

Da Da

?

Py Py

Chem

otax

is In

dex

Odorant dilution

diacetyl(AWA)

pyrazine(AWA)

benzaldehyde(AWC)

2-butanone(AWC)

10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$ 10!" 10!# 10!$0

1

0.5

0

1

0.5

* ***

***

* * ***

*

Hermaphrodite Male



XXX

odr-‐7X

XX?

odr-‐7

Male AWA neurons mediate response to Pyrazine (Py) as hermaphrodites’

!"

!#$"

!#%"

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!#'"

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!#)"

!#*"

!#+"

!#,"

$"

-./("0" -./("1" 2*-("0" 2*-("1"

******

Py 1/100C.I

MaleHerm. odr-7 Herm. odr-7 Male

Male AWA neurons mediate response to Pyrazine (Py) as hermaphrodites’

Male

AWA

PyHerm.

AWA

Py

!"

!#$"

!#%"

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!#'"

!#("

!#)"

!#*"

!#+"

!#,"

$"

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******

Py 1/100C.I


AWA neurons are not required for male response to Diacetyl (Da)

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!#'"

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!#*"

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!#,"

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Da 1/100*

C.I



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!#$"

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!#("

!#)"

!#*"

!#+"

!#,"

$"

-./("0" -./("1" 2*-("0" 2*-("1"

Da 1/100*

C.I


AWA AWC

Herm.

Da

ODR-10

AWAChou et al., 2001


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!#$"

!#%"

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!#("

!#)"

!#*"

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Da 1/100*

C.I


Male

AWCAWA

Da

AWA AWC

Herm.

Da

ODR-10



!"

!#$"

!#%"

!#&"

!#'"

!#("

!#)"

!#*"

!#+"

!#,"

$"

-./("0" -./("1" 2*-("0" 2*-("1"

Da 1/100*

C.I


Male

AWCAWA

Da

AWAAWA AWC

Herm.

Da

ODR-10



!"

!#$"

!#%"

!#&"

!#'"

!#("

!#)"

!#*"

!#+"

!#,"

$"

-./("0" -./("1" 2*-("0" 2*-("1"

Da 1/100*

C.I


Male

AWCAWA

Da

How male AWA neurons do not sense Da ?

AWAAWA AWC

Herm.

Da

ODR-10

AWA

ODR-10

Chou et al., 2001

Is the ODR-10 expression sexually different ?

Herm. ODR-10

By courtesy of Dr. Hurd (Fisher)


Herm. ODR-10Male ODR-10



Herm. ODR-10Male ODR-10

!"

#"

$!"

$#"

%!"

%#"

&!"

&#"

'!"

$" %" &" '" #"

()*+#&,-./0$!112345"67897+68)"

!"#$"%&'()"

!"#$"*+,&"

no exp.very weak

brightestODR-10::GFP

!"#$"%#&'("

ODR-10 expression is sex-specifically regulated


Herm.

Male

ODR-10::GFPDIC

Herm.

Male

AWA-feminized Male

DIC ODR-10::GFPAWA feminization

Herm.

MaleNeural sex of AWA neurons regulatessexually different ODR-10 expression

AWA-feminized Male

DIC ODR-10::GFPAWA feminization

ODR-10

active tra-1

?

Herm.

ODR-10

Male

inactive tra-1

Neural sex establishes sexually different ODR-10 expression in AWA neurons

ODR-10

active tra-1

?

Herm.

ODR-10

Male

inactive tra-1

Neural sex establishes sex difference in a target gene to generate sex difference in a common behavior

Neural sex establishes sexually different ODR-10 expression in AWA neurons

Summary

• Distinct and characteristic sex differences in C. elegans olfactory behaviors

• Neural sex generates sex differences in a sensory function

• Sexual state of a single sensory neuron AWA establishes sex difference in a target gene expression

- a potential direct substrate of sex difference in a common sensory behavior

Genes

Circuit

Behavior

How do changes in gene expressions modify behaviors?

Sex

Genes

Circuit

Behavior

How do changes in gene expressions modify behaviors?

Sex

Environmental cues

Species

Implications on sex differences in the vertebrate nervous system

Y chromosome specific sex regulators,

the number of X chromosomes

Target genes (neuronal death, dendritic growth, ...)

Sex difference in the brain and behavior

Thank You

Thesis CommitteeRobert S. Freeman

Oliver Hobert (Columbia Univ.)Kathy W. Nordeen

Reagents/suggestionsCori Bargmann (Rockefeller Univ.)

Hillel Schwartz and Robert Horvitz (MIT)Jamie White and Erik Jorgensen (Univ. of Utah)

Caenorhabditis Genomics Center

Interdepartmental Graduate Program in NeuroscienceCenter for Neural Disease and Development

Autism SpeaksNIH (1R01GM086456-01)

Portman LabDouglas S. Portman, Ph.D.Margaret CasazzaDaryl Hurd, Ph.D. (Fisher)Stefani McGregor

Renee Miller, Ph.D.William MowreyNeda MuzaffarEdward VuongRiley O’Neil

Former membersKwi Lee (UB) Adam Mason, Ph.D. (Siena)

.

Presentations & Public Speaking

Thesis defense talk KyungHwa (Kirsten) Lee 2009