ORIGINAL RESEARCH ARTICLE
published: 25 Sep embe 2014
doi: 10.3389/ nana.2014.00106
Dog and mouse: owa d a balanced iew o he
mammalian ol ac o y sys em
A hu W. Ba ios , Pablo Sánchez-Quin ei o and Ignacio Salaza *
Uni o Ana omy and Emb yology, Depa men o Ana omy and Animal P oduc ion, Facul y o Ve e ina y, Uni e si y o San iago de Compos ela, Lugo, Spain
Edi ed by:
Pablo Chame o, Uni e si y o
Saa land, Ge many
Re iewed by:
An onio Pe ei a, Fede al Uni e si y
o Rio G ande do No e, B azil
Maud Rimbaul , Na ional Ins i u es
o Heal h, USA
*Co espondence:
Ignacio Salaza , Uni o Ana omy and
Emb yology, Depa men o
Ana omy and Animal P oduc ion,
Facul y o Ve e ina y, Uni e si y o
San iago de Compos ela, A
Ca ballo Cale o s/n, 27002 Lugo,
Spain
e-mail: [email p o ec ed]
Al hough he mos in ensi ely s udied mammalian ol ac o y sys em is ha o he mouse,
in which ol ac o y chemical cues o one kind o ano he a e de ec ed in ou di e en
nasal a eas [ he main ol ac o y epi helium (MOE), he sep al o gan (SO), G ünebe g’s
ganglion, and he senso y epi helium o he ome onasal o gan (VNO)], he ex ao dina ily
sensi i e ol ac o y sys em o he dog is also an impo an model ha is inc easingly used,
o example in genomic s udies o species e olu ion. He e we desc ibe he opog aphy
and ex en o he main ol ac o y and ome onasal senso y epi helia o he dog, and we
epo inding no s uc u es equi alen o he G ünebe g ganglion and SO o he mouse.
Since we examined adul s, newbo ns, and e uses we conclude ha hese la e s uc u es
a e absen in dogs, possibly as he esul o eg ession o in olu ion. The absence o
a ome onasal componen based on VR2 ecep o s sugges s ha he VNO may be
unde going a simila in olu iona y p ocess.
Keywo ds: ol ac o y epi helium, ol ac o y subsys ems, mo phology, e olu ion, dog
INTRODUCTION
The dog is inc easingly app ecia ed in biomedical esea ch as
a species ha , unlike pu pose-b ed labo a o y animals, sha es
he gene ic, and clinical a ie y o human pa ien s (Ka lsson
and Lindblad-Toh, 2008). I s nasal ca i y has been s udied om
a ious poin s o iew. Ana omically, G aege ’s pape (G aege ,
1958) is conside ed he classical e e ence. Physiologically, a en-
ion has ecen ly ocused on nasal ai low pa e ns (C a en e al.,
2007, 2010). Clinically, he p esen a ion, diagnosis, p ognosis,
and ea men o umo s is a majo cu en conce n (McEn ee,
2004; Tu ek and Lana, 2012; Mason e al., 2013), bu he ol ac-
o y mucosa o he nasal ca i y has also a ac ed clinical in e es
because o i s unique main enance o a popula ion o basal
cells suppo ing he con inual egene a ion o ol ac o y sen-
so y neu ons (OSNs) (G aziadei and Mon i-G aziadei, 1979);
he in aspinal implan a ion o cells de i ed om au ologous
ol ac o y mucosa cul u es has in ac ecen ly been success ul in
amelio a ing he e ec s o spinal co d inju ies in companion dogs
(G ange e al., 2012).
In he mouse, he animal in which he mammalian ol ac-
o y sys em has been mos in ensi ely s udied, he nasal mucosa
ea u es ou sepa a e ol ac o y a eas: he main ol ac o y epi he-
lium (MOE), he sep al o gan (SO), he ganglion o G ünebe g
(GG), and he ome onasal senso y epi helium [VNsE, no o
be con used wi h he ome onasal o gan (VNO) o which i
o ms a pa ] (B ee e al., 2006; Munge e al., 2009; Ma,
2010; Ba ios e al., 2014). These ou senso y a eas can be
conside ed as he poin s o en y o ou ol ac o y subsys-
ems (OSbS), he in eg a ion o which a highe le els is a
ocus o cu en esea ch. Howe e , his ou -subsys em scheme
is by no means exhibi ed by all mammals, o e en by all
mac osma ic mammals (Salaza and Sánchez-Quin ei o, 2009).
In he wo k desc ibed he e we examined i s alidi y o he
dog, a no o iously mac osma ic animal. We ound ha he dog
has no GG o SO, and ha i s VNO shows signs o simila
in olu ion.
MATERIALS AND METHODS
ANIMALS
The dogs s udied we e 31 male o emale mesa icephalic adul s,
17 newbo n males o emales om ou di e en li e s, and 16
e uses ob ained on days 30, 35, o 40 o ges a ion. Mos we e
Ge man Shephe ds o mong els de i ed he e om, and all we e
mesa icephalic. All we e ob ained legally h ough he dissec ing
and pos -mo em ooms and Depa men o Clinical Science o
ou acul y and we e ea ed in acco dance wi h Spanish and EU
legisla ion o he ca e and handling o animals in esea ch (RD
223/1998, 86/609/EEC) and wi h he guidelines o he Uni e si y
o San iago de Compos ela Bioe hical Commi ee. The heads o
all animals we e in ac and showed no clinical o pos -mo em
e idence o neu ological disease; all we e p ocessed as speci ied
below as soon a e dea h as was possible.
PROCESSING OF SAMPLES AND TISSUE SECTIONS
Using adi ional ana omical echniques, 22 adul heads we e
ca e ully p epa ed by dissec ion and mic o-dissec ion— om ou -
side o inside— o a o d iews o he la e al and medial walls o
he nasal ca i y and la e al and medial iews o he u bina es.
Views we e sys ema ically eco ded in pho og aphs and d aw-
ings, and he ch oma ic cha ac e is ics o he mucosa we e no ed.
The sepa a e componen s o he u bina e complex we e hen
dissec ed and p epa ed.
Se en puppy heads we e simila ly p epa ed excep o he inal
dissec ion o he u bina e complex.
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NEUROANATOM
Y
Ba ios e al. Ol ac o y epi helia o he dog
T ans e se sec ions o uni o m hickness we e cu on a
polys y ene block om wo adul heads ha had been washed and
ozen ollowing app op ia e cleaning, ixa ion by imme sion in
10% o maldehyde o 96 h, and emo al o he mandibles and
associa ed s uc u es.
Ten puppy heads we e p epa ed o his ological examina ion as
ollows. Eigh heads (g oup 1) we e ixed by imme sion in neu al
bu e ed o maldehyde, whe e hey emained un il use, and wo
(g oup 2) we e imme sed in Bouin’s ixa i e o 24 h and hen
ans e ed o 70% alcohol. Fo examina ion o he whole nasal
ca i y (mainly wi h a iew o delimi ing he MOE), wo g oup
1 heads we e decalci ied in Shandon TBD-1 apid decalci ie
(The mo, Pi sbu gh, PA) and embedded in one piece, app o-
p ia ely o ien ed, in pa a in wax, a e which se ial ans e se
sec ions 8–10 μm hick we e cu . 710 al e na e sec ions om one
o hese heads, and 710 co esponding sec ions om he o he ,
we e ans e ed o slides and s ained wi h hema oxylin-eosin
(HE). The emaining eigh heads (six om g oup 1 and he wo
g oup 2 heads) we e p epa ed, sec ioned and s ained in he same
way, excep ha be o e sec ioning he nasal ca i y was di ided
ans e sally in o h ee blocks o mo e o less equal leng h.
All e al heads we e p ocessed o his ological examina ion in
he same way as he puppy heads, wi h he main goal o sc u i-
nizing he egions in which he GG and SO we e expec ed o be
ound, i p esen . The pos e io nasal ca i y was also s udied.
Owing o he di icul y o his ological p epa a ion o he whole
adul nasal ca i y, he ollowing sub egions o he emaining se en
adul heads we e excised, decalci ied, and embedded in pa a in
wax o sec ioning and subsequen s aining o he sec ions wi h
HE o an ibodies (see below): (i) ou le els o he nasal sep um;
and (ii) he indi idual u bina es.
IMMUNOHISTOCHEMISTRY
Immunohis ochemical s udies we e pe o med using an ibodies
agains ol ac o y ma ke p o ein (OMP) (Wako Chemicals, 1:500
dilu ion) and he G-p o eins Gαi2 (San a C uz Bio echnology,
1:100) and Gαo(San a C uz Bio echnology and Medical &
Biological Lab Co., 1:100). Sec ions we e dewaxed in xylene,
ehyd a ed, and successi ely incuba ed (1) o 30 min a oom
empe a u e in PBS con aining 5% no mal ho se se um and 2%
bo ine se um albumin, (2) o 24 h a 4◦Cinp ima yan ibody
solu ion, (3) o 1 h in bio inyla ed seconda y an ibody solu ion,
and (4) o 2 h in a solu ion o a idin-bio in-ho se adish pe -
oxidase complex (ABC Vec as ain eagen ); a e which s anda d
p ocedu es o isualiza ion o he ho se adish pe oxidase com-
plex wi h 3,3-diaminobenzidine we e ollowed, and he sec ions
we e dehyd a ed h ough alcohols, clea ed in xylene, and co e -
slipped. Sec ions o o malin- o Bouin- ixed canine and mu ine
ol ac o y bulbs we e used as con ol issues.
IMAGE ACQUISITION AND PROCESSING
Digi al images we e cap u ed using a Ka l Zeiss Axiocam MRc5
digi al came a. When necessa y, Adobe Pho oshop 6.0 (Adobe
Sys ems, San Jose, CA) was used o adjus con as and b igh ness
o equilib a e ligh le els, and/o o c op, esize, and o a e he
images o p esen a ion; no addi ional digi al image manipula ion
was pe o med.
FIGURE 1 | La e al iew o he nasal sep um o an adul dog, showing
he di e ence in colo be ween senso y (yellow-b own) and
espi a o y ( ed-o ange) mucosa. The ec angle ames he
ome ona asal o gan. Scale ba : 2 cm (see Figu e S1).
RESULTS
The nasal ca i ies o m a bila e ally symme ic pai lanking he
nasal sep um. Figu e 1 and Figu e S1 show iews o he la e al
and medial ca i y walls and o he u bina e complex wi hin he
ca i y; Figu e 2 la e al and medial iews o he u bina e complex
wi hou he walls o he ca i y; and Figu e S2 la e al and medial
iews o each sepa a e componen o he u bina e complex. This
comp ises six la e al ec o u bina es, ou medial endo u bina es,
and he en al concha; he do sal concha is a os al p ojec ion
o endo u bina e I, and he middle concha pa o endo u bina e
II. Pa s o ec o u bina es 2 and 3 p ojec o he on al sinus.
T ans e se sec ions (Figu e 3 and Figu e S3) clea ly show he
ap ness o he e m “complex.”
In he mucosa lining he nasal ca i y, colo di e en ia es
be ween he espi a o y and ol ac o y epi helia, he o me
exhibi ing shades o ed o o ange, he la e shades o yellow
o b own (Figu e 1 and Figu e S1). His ological examina ion o
selec ed zones o he nasal sep um and o he isola ed u bina es
2, 3, II, and III (Figu e 4 and Figu e S4) shows he ansi ion
be ween he wo ypes o epi helia (Figu e 4A), and also di -
e ences among di e en a eas o senso y mucosa in ega d o
he hicknesses o epi helium and lamina p op ia and he el-
a i e hicknesses o he laye s o he h ee epi helial cell ypes
(sus en acula , basal, and neu onal) (Figu es 4B–E and Figu e
S4). Immunohis ochemically, he ma u e neu ons and hei api-
cal p ojec ions o hese zones we e s ained by an i-OMP, and
he ne e bundles in he lamina p op ia by bo h an i-OMP and
an i-Gα0,bu an i-G
αi2 s ained no hing speci ically (Figu e 5 and
Figu e S5). S aining consis en wi h hese esul s was obse ed in
he ol ac o y bulbs o dogs and mice used as con ols ( esul s no
shown).
The VNO, en eloped in a ca ilaginous lamina, lies adjacen o
he nasal sep um (Figu e 1). Since he VNsE is loca ed in e nally,
o ming he cen al le els o he medial wall o he VNO duc , i s
mac oscopic display would be di icul , equi ing a p ecise, some-
wha cu ilinea longi udinal sec ion h ough he ca ilage and
i s con en ( he duc and he o he so issues ha su ound i ).
His ologically, he VNsE is composed o basal cells, ecep o neu-
ons and suppo ing cells, while he an e io pa o he VNO
duc ea u es s a i ied squamous epi helium and he pos e io
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Ba ios e al. Ol ac o y epi helia o he dog
FIGURE 2 | Pho og aphs and schema ic d awings o he u bina e
complex in la e al (A) and medial (B) iews. DNC, do sal nasal concha;
MNC, middle nasal concha; VNC, en al nasal concha. Ec o u bina es a e
iden i ied in he d awings by A abic nume als (1–6) and shades o g een,
endo u bina es by oman nume als (I–IV) and shades o pink. Scale ba :
2 cm (see Figu e S2).
pa simple columna epi helium (Figu e 6 and Figu e S6). The
immunohis ochemical ea u es o he VNsE ha e ecen ly been
epo ed elsewhe e (Salaza e al., 2013) and a e commen ed on
below in he Discussion.
The abo e desc ip ions all e e o adul specimens. In new-
bo ns he on al sinus and ec o u bina e 6 a e missing, and
ec o u bina e 1 is e y small (Figu e 7). The MOE canno usu-
ally be dis inguished ch oma ically om espi a o y epi helium,
and mus be iden i ied his ologically. Figu e S7 shows he e -
i o y i occupies as de e mined by examina ion o se ies o
ans e se sec ions, which also show he simplici y and small a ea
o he neona al u bina es in compa ison wi h hose o adul s
(Figu e S8).
In nei he adul s no newbo ns did we ind any s uc u e wi h
he cha ac e is ics de ining he SO and GG in mice (Ba ios e al.,
2014). Among ou 16 e al specimens (Figu e 8 shows sec ions
FIGURE 3 | T ans e se ozen sec ion o he nasal ca i y. D, do sal nasal
concha. Ec o u bina es a e iden i ied by A abic nume als (1–5) and
endo u bina es by oman nume als (I–IV). Scale ba : 2 cm (see Figu e S3).
FIGURE 4 | (A) Hema oxylin-eosin-s ained longi udinal sec ion showing he
ansi ion (a owed) om he espi a o y o he senso y epi helium.
(B–E) Hema oxylin-eosin s ained ans e se sec ions showing he mucosa
o ec o u bina e 2 (B), ec o u bina e 3 (C), endo u bina e III (D),and he
nasal sep um (E). Yellow ba s indica e senso y epi helium; blue ba s, lamina
p op ia; and whi e a ows, bone. 1, suppo ing cells; 2, neu ons; 3, basal
cells. Scale ba s: (A) 2 mm; (B–E) 100 μm (see Figu e S4).
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Ba ios e al. Ol ac o y epi helia o he dog
FIGURE 5 | T ans e se sec ions o endo u bina e II s ained wi h
an i-OMP (A) and an i-Gαo(B), showing labeling o ma u e neu ons (in
A) and ne e bundles (a owed) o he ol ac o y mucosa. Yellow ba s
indica e senso y epi helium; blue ba s, lamina p op ia; he as e isk, bone.
Scale ba s: (A) 100 μm; (B) 1 mm (see Figu e S5).
om one) he e was one specimen in which he possible exis ence
o GG cells was sugges ed by he p esence o a ne e su ounded
by essels in he egion homologous o he mouse GG, bu OMP
ailed o label any cells in his a ea.
DISCUSSION
Among mammalian ol ac o y sys ems, he mos ex ensi ely,
and in ensi ely s udied has been ha o he mouse—a ci -
cums ance i sha es wi h many o he o he cha ac e is ics o
his animal (Paigen, 1995). I comp ises ou majo subsys-
ems (OSbS) s imula ed ia ou di e en a eas o he nasal
mucosa: he MOE, he VNsE, he SO, and he GG (Ba ios
e al., 2014). A i e-subsys em scheme eme ges i he di e ence
be ween ome onasal subsys ems based on semiochemical ecep-
o ypes VR1 and VR2 is aken in o accoun (Ba ios e al.,
2014). Al hough nume ous s udies o he canine nasal mucosa
ha e been published (Lau uschkus, 1942; Mülle , 1955; Neuhaus,
1955; Adams and Ho chkiss, 1983; Ka oi e al., 2010), we a e
unawa e o any p e ious sys ema ic sea ch o hese ou o
i e OSbS in he dog. The indings epo ed abo e, oge he
wi h ou p e ious obse a ion ha he canine ome onasal sys-
em binds an i-Gαi2 bu no an i-Gαoan ibodies (Salaza e al.,
2013), show ha he dog has only he main and ome onasal
FIGURE 6 | Hema oxylin-eosin-s ained ans e se sec ion o he
ome onasal o gan (VNO, amed); le is la e al, up is do sal. The
as e isk indica es he lumen o he ome onasal duc ; (1) ne es; (2)
essels; and (3) a gland. The VNO is pa ially su ounded by
connec i e issue (4) and ca ilage (whi e a ow). Scale ba : 500 μm
(see Figu e S6).
subsys ems, and ha he la e is in all p obabili y en i ely
VR1-based.
Ou obse a ions o he MOE show di e en a eas o di e
conside ably, especially as ega ds he hickness o he neu on
laye and hence he su ace densi y o neu ons, e en on a sin-
gle u bina e.Howe e ,wewe eunable oo ganize heobse ed
a ia ion in a classi ica ion o mucosal ypes, o o ela e ou
obse a ions o he wo- ype classi ica ion p oposed p e iously
(Bock e al., 2009) on he basis o mo phological cha ac e is ics,
neu on u no e , and immuno eac i i y.
Whe eas he mu ine ome onasal sys em exp esses he VR1-
associa ed p o ein Gαi2 in he apical laye o he VNsE and he
an e io hal o he accesso y ol ac o y bulb (AOB), and he VR2-
associa ed p o ein Gαoin he basal laye o he VNsE and he
pos e io hal o heAOB(Ba ios e al., 2014), he canine sys-
em does no exp ess Gαo, and exp esses Gαi2 h oughou he
AOB as well as in he VNsE (Salaza e al., 2013). This beha -
io is in keeping wi h epo ed ailu e o ind unc ional VR2
genes in he canine genome (Young and T ask, 2007). Gi en hei
p esence in opossum (Young and T ask, 2007) and oden s (Ishii
and Mombae s, 2011), hei absence om he dog (and cow
and p ima es) (Young and T ask, 2007)mus be he esul o an
in olu iona y p ocess (Salaza and Sánchez-Quin ei o, 2009).
Reg essi e p ocesses, whe he e olu iona y o on ogenic, seem
also o ha e led o he absence o bo h SO and GG om he
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Ba ios e al. Ol ac o y epi helia o he dog
FIGURE 7 | The nasal ca i y o he newbo n dog. (A) La e al iew o he u bina e complex. (B) La e al iew o he nasal sep um. (C) Medial iew o he
u bina e complex. (D) Medial iew o he la e al wall. Scale ba : 1 cm (see Figu e S7).
canine nasal ca i y. Con a y o such equen ly made asse ions
as ha “ he mammalian nose con ains se e al dis inc chemosen-
so y o gans, including he... MOE, he... VNO and he SO”
(Tian and Ma, 2004), he SO, hough p esen in ma supials,
and in mice, a s, and abbi s, is absen om he e e and
he ca as well as he dog, ( hough epo edly p esen in e al
ca ) (B eipohl e al., 1983; Kociáno á e al., 2006; Ma, 2010).
Simila ly, s a emen s o he e ec ha G ünebe g ound he
GG “in all mammals examined, including humans” (Tian and
Ma, 2004) igno e he ac ha he ac ually epo ed de ini ely
obse ing i in only h ee o he 13 species he s udied: mouse,
a , and hams e (G ünebe g, 1973). In ou species (squi el,
guinea pig, sh ew, and a sie —no e he wo oden s) i seemed
o be absen ; and in he emaining six, including Homo sapi-
ens, i s p esence was unce ain. Fu he mo e, he only s udied wo
species as adul s (mouse and sh ew) and h ee mo e as new-
bo ns ( a , mole, and guinea-pig); all his o he specimens we e
emb yos o e uses, and he speci ically sugges ed ha in many
species he ganglion, hough possibly p esen in hese ea ly s ages,
may eg ess du ing p ena al de elopmen —a p ocess he de ini ely
asse ed o he accoon on he basis o examina ion o ou e al
s ages.
Tha he dog lacks wo o he ol ac o y epi helia o he mouse
(SO and GG), and has an appa en ly less complex o m o a
hi d ( he VNsE), may seem su p ising in iew o i s no o iously
mac osma ic na u e. I may be he case ha he la ge size o
he canine nasal ca i y allows physical sepa a ion o play a la ge
pa in he dog’s disc imina ion among odo s han is possible
in he mouse (Schoen eld and Cleland, 2005); in his espec ,
i mus be bo ne in mind ha ou dogs we e mainly Ge man
Shephe ds o o Ge man Shephe d descen , so he possibili y
ha he SO and GG may be p esen in o he b eeds canno be
absolu ely uled ou . Ano he possibili y is ha in spi e o he
sensi i i y o he dog’s sense o smell, and i s abili y o lea n
o de ec un amilia subs ances by ol ac ion, i s li es yle p io o
i s domes ica ion some 15,000 yea s ago (Leona d e al., 2002;
Sa olainen e al., 2002) equi ed ecogni ion o a smalle ange
o ol ac o y cues han did ha o he mouse. In his ega d, he
dog is epo ed o ha e 811 unc ional ol ac o y ecep o genes
as agains he 1035 o he mouse (Shi and Zhang, 2009; Niimu a,
2012).
Since i s domes ica ion, he dog has o cou se been he
objec o in ensi e a i icial selec ion p ocesses ha ha e a -
iously pu sued he enhancemen o mo phological, beha io al
and physiological ai s ( ega ding he mechanis ic di e ences
among hese di e en ypes o modi ica ion, see Ca oll, 2005,
2008; Liao e al., 2010). C ea ing he app oxima ely 400 b eeds
o dog now es ima ed o exis (Ame ican Kennel Club, 2006)
has al e ed he genome and i s ealiza ion in many ways (Wayne
and on Hold , 2012), i is commonly hough ha dogs col-
lec i ely exhibi g ea e mo phological a ia ion han any o he
land mammal (Os ande , 2012), and hese al e a ions ha e been
igo ously in es iga ed, especially since he publica ion o he
genome (Lindblad-Toh e al., 2005). Mos o hese s udies ha e
conce ned he mo phological ai s ha de ine b eeds—body size,
coa , leg leng h, and wid h, skull shape, e c. (Boyko e al., 2010;
Pa ke e al., 2010; Schoenebeck and Os ande , 2013), bu o h-
e s ha e add essed ol ac o y ecep o genes, inding bo h ma ked
uni o mi y a he gene amily le el, and signi ican a ia ion a
lowe le els (Issel-Ta e and Rine, 1996; Olende e al., 2004;
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Ba ios e al. Ol ac o y epi helia o he dog
FIGURE 8 | Hema oxylin-eosin-s ained ans e se sec ions o he nasal
ca i y o a newbo n, a he le els co esponding o he mu ine
ganglion o G ünebe g (A) and sep al o gan (C). (B,D) De ails o (A,C),
espec i ely. Scale ba s: (A) 500 μm; (B) 250 μm; (C) 1000μm; (D) 500 μm.
Tache e al., 2005; Robin e al., 2009; Chen e al., 2012; De ien
e al., 2012; Quignon e al., 2012). This pa e n sugges s ha
ou main esul s— he absence o SO, GG, and a VR2-based
ome onasal subsys em—seem likely o be gene alizable o b eeds
o he han Ge man Shephe ds, bu con i ma ion is equi ed.
Ligh would also be h own on his issue by a s udy o wol es o
de e mine whe he he absence o hese subsys ems is a esul o
domes ica ion.
In he s udy o ol ac ion, as in o he ields (Ka lsson and
Lindblad-Toh, 2008), he dog is p o ing o be a mine o in o -
ma ion, and is leading o a much mo e balanced iew o he
mammalian ol ac o y sys em han was p omo ed by exclusi e
a en ion o he mouse model.
AUTHOR CONTRIBUTIONS
Ignacio Salaza designed he esea ch and w o e he pape . A hu
W. Ba ios, and Pablo Sánchez-Quin ei o pe o med he wo k.
A hu W. Ba ios, Pablo Sánchez-Quin ei o, and Ignacio Salaza
analyzed and discussed he da a.
ACKNOWLEDGMENTS
We hank all he colleagues who pa icipa ed in his wo k,
especially o J. Rod iguez and L. A edillo; J. Cas iñei a o
echnical assis ance; and I. C. Coleman o e ising he inal
English e sion. A hu W. Ba ios hanks he Spanish Minis y
o Fo eign A ai s o an MAEC-AECID g an . P i a e inan-
cial suppo is g a e ully acknowledged. We eg e ha we we e
no able o ci e all o he pape s ha ha e con ibu ed o his
ield.
SUPPLEMENTARY MATERIAL
The Supplemen a y Ma e ial o his a icle can be ound
online a : h p://www. on ie sin.o g/jou nal/10.3389/ nana.
2014.00106/abs ac
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Con lic o In e es S a emen : The au ho s decla e ha he esea ch was con-
duc ed in he absence o any comme cial o inancial ela ionships ha could be
cons ued as a po en ial con lic o in e es .
Recei ed: 30 June 2014; accep ed: 09 Sep embe 2014; published online: 25 Sep embe
2014.
Ci a ion: Ba ios AW, Sánchez-Quin ei o P and Salaza I (2014) Dog and mouse:
owa d a balanced iew o he mammalian ol ac o y sys em. F on . Neu oana . 8:106.
doi: 10.3389/ nana.2014.00106
This a icle was submi ed o he jou nal F on ie s in Neu oana omy.
Copy igh © 2014 Ba ios, Sánchez-Quin ei o and Salaza . This is an open-access
a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion License
(CC BY). The use, dis ibu ion o ep oduc ion in o he o ums is pe mi ed, p o ided
he o iginal au ho (s) o licenso a e c edi ed and ha he o iginal publica ion in his
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