Aula de Biologia do desenvolvimento

Prévia do material em texto

Biologia  do  Desenvolvimento	
Neurulação	
Prof.  Pedro  Vale  de  Azevedo  Brito	
Ectoderme  em  Vertebrados	
A  ectoderme  em  vertebrados  origina  3  estruturas:	
1)  Placa  Neural    è Tubo  Neural  è  Sistema  Nervoso  Central	
2)  Epiderme  e  anexos	
3)  Crista  Neural	
!
"#$!%$&'!(#)*$!+,!-)*'./0)'1+%! 1%2+02$*! '#$! 1%2+0/'1+%!+,! '#$!3).-1%)0!4+%$!5$00*!6#10$!
'#$! )%13)0! 5$00*! /%7$.-+! $(18+09! )%7! 5+%2$.-$! )'! '#$! 80)*'+(+.$! :;1-/.$! <=>?@A!BC>!D#$%! '#$!
31-.)'1%-!3).-1%)0!5$00*!.$)5#!'#$!dorsal lip!+,!'#$!80)*'+(+.$A!'#$9!'/.%!1%6).7!)%7!'.)2$0!)0+%-!
'#$!1%%$.!*/.,)5$!+,!'#$!+/'$.!)%13)0!#$31*(#$.$!5$00*>!"#/*A!'#$!5$00*!5+%*'1'/'1%-!'#$!01(!+,!'#$!
80)*'+(+.$! ).$! 5+%*')%'09!5#)%-1%->!"#$! ,1.*'! 5$00*! '+! 5+3(+*$! '#$!7+.*)0! 80)*'+(+.$! 01(! ).$! '#$!
8+''0$!5$00*!'#)'!1%2)-1%)'$7!'+!,+.3!'#$!0$)71%-!$7-$!+,!'#$!).5#$%'$.+%>!"#$*$!5$00*!0)'$.!8$5+3$!
'#$!(#).9%-$)0!5$00*!+,! '#$!,+.$-/'>!E*! '#$*$!,1.*'!5$00*!()**! 1%'+! '#$! 1%'$.1+.!+,! '#$!$38.9+A! '#$!
7+.*)0! 80)*'+(+.$! 01(! 8$5+3$*! 5+3(+*$7! +,! 5$00*! '#)'! 1%2+0/'$! 1%'+! '#$! $38.9+! '+! 8$5+3$! '#$!
prechordal plate! :'#$! (.$5/.*+.! +,! '#$! #$)7! 3$*+7$.3C>! "#$! %$&'! 5$00*! 1%2+0/'1%-! 1%'+! '#$!
$38.9+!'#.+/-#!'#$!7+.*)0!80)*'+(+.$!01(!).$!5)00$7!'#$!chordamesoderm!5$00*>!"#$*$!5$00*!6100!
,+.3! '#$! notochordA! )! '.)%*1$%'! 3$*+7$.3)0! F8)5G8+%$F! '#)'! (0)9*! )%! 13(+.')%'! .+0$! 1%!
71*'1%-/1*#1%-!)%7!()''$.%1%-!'#$!%$.2+/*!*9*'$3>!
E*! '#$! %$6! 5$00*! $%'$.! '#$! $38.9+A! '#$! 80)*'+5+$0! 1*! 71*(0)5$7! '+! '#$! *17$! +((+*1'$! '#$!
7+.*)0!01(!+,!'#$!80)*'+(+.$>!H$)%6#10$A!'#$!80)*'+(+.$!01(!$&()%7*!0)'$.)009!)%7!2$%'.)009!)*!'#$!
(.+5$**$*! +,! 8+''0$! 5$00! ,+.3)'1+%! )%7! 1%2+0/'1+%! 5+%'1%/$! )8+/'! '#$! 80)*'+(+.$>! "#$!617$%1%-!
80)*'+(+.$! F5.$*5$%'F! 7$2$0+(*! 0)'$.)0! 01(*! )%7! ,1%)009! )! 2$%'.)0! 01(! +2$.! 6#15#! )771'1+%)0!
3$*+7$.3)0! )%7! $%7+7$.3)0! (.$5/.*+.! 5$00*! ()**>! ! D1'#! '#$! ,+.3)'1+%! +,! '#$! 2$%'.)0! 01(A! '#$!
80)*'+(+.$! #)*! ,+.3$7! )! .1%-! ).+/%7! '#$!
0).-$!$%7+7$.3)0!5$00*!'#)'!.$3)1%!$&(+*$7!
+%!'#$!2$-$')0!*/.,)5$>!
!
!
!
!
!
"#$!%&'(')'*$!+)&$,-!.$/'0$+!)#$!,1$+!2/!)#$!$(3&425!6)!$1)$0.+!/&2(!posterior!)2!anterior7!
('8&,)'08!9$::+!$0)$&!)#&2;8#!')+!dorsal!+'.$!,0.!(2*$!)2!')+!ventral!+'.$7!,0.!')!+$%,&,)$+!)#$!left!
%2&)'20! 2/! )#$! $(3&42! /&2(! )#$! right.! "#2+$! $:$($0)+! 9:2+$! )2! )#$! +)&$,-! <'::! 3$! )#$!medial!
=9$0)&,:>! +)&;9);&$+?! <#':$! )#2+$! /,&)#$&! /&2(! ')! <'::! 3$! )#$! distal! =:,)$&,:>! +)&;9);&$+! =@'8;&$!
AA5ABCDE>5!
F+! 9$::+! 920*$&8$! )2! /2&(! )#$!
%&'(')'*$! +)&$,-?! ,! .$%&$++'20! /2&(+!
<')#'0! )#$! +)&$,-5! "#'+! .$%&$++'20! '+!
9,::$.!)#$!primitive groove?!,0.!')!+$&*$+!
,+! ,0! 2%$0'08! )#&2;8#! <#'9#! ('8&,)'08!
9$::+! %,++! '0)2! )#$! 3:,+)292$:5! "#;+?! )#$!
%&'(')'*$! 8&22*$! '+! ,0,:282;+! )2! )#$!
,(%#'3',0!3:,+)2%2&$5!F)!)#$!,0)$&'2&!$0.!
2/! )#$! %&'(')'*$! +)&$,-! '+! ,! &$8'20,:!
)#'9-$0'08! 2/! 9$::+! 9,::$.! )#$! primitive 
knot!2&!Hensen's node5!"#$!9$0)$&!2/!)#'+!
02.$!920),'0+!,!/;00$:D+#,%$.!.$%&$++'20!
=+2($)'($+!9,::$.! )#$!primitive pit>!
)#&2;8#!<#'9#!9$::+!9,0!%,++!'0)2!)#$!
3:,+)292$:5! G$0+$0H+! 02.$! '+! )#$!
/;09)'20,:!$I;'*,:$0)!2/!)#$!.2&+,:!:'%!
2/!)#$!,(%#'3',0!3:,+)2%2&$!='5$5?!)#$!
2&8,0'J$&>! ,0.! )#$! /'+#! $(3&420'9!
+#'$:.5!
!
F+! +220! ,+! )#$! %&'(')'*$! +)&$,-! #,+!
/2&($.?!$%'3:,+)!9$::+!3$8'0!)2!('8&,)$!)#&2;8#!')!,0.!'0)2!)#$!3:,+)292$:!=@'8;&$!AA5AA>5!! !!!!!!!!
"#$!%&'(')'*$!+)&$,-!#,+!,!920)'0;,::4!9#,08'08!9$::!%2%;:,)'205!C$::+!('8&,)'08!)#&2;8#!G$0+$0H+!
02.$!%,++!.2<0!'0)2!)#$!3:,+)292$:!,0.!('8&,)$!,0)$&'2&:4?!/2&('08!/2&$8;)?!#$,.!($+2.$&(?!,0.!
02)29#2&.7! 9$::+! %,++'08! )#&2;8#! )#$! :,)$&,:! %2&)'20+! 2/! )#$! %&'(')'*$! +)&$,-! 8'*$! &'+$! )2! )#$!
(,K2&')4! 2/! $0.2.$&(,:! ,0.!($+2.$&(,:! )'++;$+! =L9#2$0<2:/! $)! ,:5! AMMN>5!O0:'-$! )#$!Xenopus!
($+2.$&(?!<#'9#!('8&,)$+!,+!+#$$)+!2/!9$::+! '0)2! )#$!3:,+)292$:?!9$::+!$0)$&'08! )#$! '0+'.$!2/! )#$!
,*',0! $(3&42! '08&$++! ,+! '0.'*'.;,:+! ,/)$&! ;0.$&82'08! ,0! $%')#$:',:D)2D($+$09#4(,:!
)&,0+/2&(,)'205!F)!G$0+$0H+!02.$!,0.!)#&2;8#2;)!)#$!%&'(')'*$!+)&$,-?!)#$!3&$,-.2<0!2/!)#$!3,+,:!
:,('0,!,0.! )#$! &$:$,+$!2/! )#$+$!9$::+! '0)2! )#$!$(3&42! '+! )#2;8#)! )2!3$!,992(%:'+#$.!34!scatter 
factor?!,!AMBD-P,!%&2)$'0!+$9&$)$.!34!)#$!9$::+!,+!)#$4!$0)$&!)#$!+)&$,-!=L)$&0!$)!,:5!AMMB7!P$Q;9,!
$)!,:5!AMMM>5!L9,))$&!/,9)2&!9,0!920*$&)!$%')#$:',:!+#$$)+!'0)2!($+$09#4(,:!9$::+!'0!+$*$&,:!<,4+?!
,0.! ')! '+!%&23,3:4! '0*2:*$.!32)#! '0!.2<0&$8;:,)'08!ED9,.#$&'0!$1%&$++'20!,0.! '0!%&$*$0)'08!ED
9,.#$&'0!/&2(!/;09)'20'08!!
R'8&,)'20!)#&2;8#!)#$!%&'(')'*$!+)&$,-S!/2&(,)'20!2/!$0.2.$&(!,0.!($+2.$&(5!
"#$! /'&+)! 9$::+! )2! ('8&,)$! )#&2;8#! G$0+$0H+! 02.$! ,&$! )#2+$! .$+)'0$.! )2! 3$92($! )#$!
%#,&408',:!$0.2.$&(!2/! )#$!/2&$8;)5!T09$!'0+'.$!)#$!3:,+)292$:?! )#$+$!$0.2.$&(,:!9$::+!('8&,)$!
,0)$&'2&:4!,0.!$*$0);,::4!.'+%:,9$!)#$!#4%23:,+)!9$::+?!9,;+'08!)#$!#4%23:,+)!9$::+!)2!3$!920/'0$.!
)2!,!&$8'20!'0!)#$!,0)$&'2&!%2&)'20!2/!)#$!,&$,!%$::;9'.,5!!
!
12. The central nervous system and the epidermis 
"#$%&! '(! )*+$%)(! &$*! ,-(&! '.&+'/0'./! 10*(&'-.! -2! %33! '(! 4$*&$*+! &$*! 5+%'.! '(! )-4*+203!
*.-0/$!&-!(-36*! &$*!)+-53*,!-2! '&(!-4.!7+*%&'-.8"!9-!:+*/-+!;'7$*3*! <=>>?@!*.A*A!%! +*6'*4!-2!
+*(*%+7$!-.!,%,,%3'%.!5+%'.!A*6*3-),*.&8!B$*!7-.(&+07&'-.!-2!%.!-+/%.!&$%&!)*+7*'6*(C!&$'.D(C!
3-6*(C! $%&*(C! +*,*,5*+(C! 7$%./*(C! 2--3(! '&(*32C! %.A! 7--+A'.%&*(! -0+! 7-.(7'-0(! %.A! 0.7-.(7'-0(!
5-A'3E! )+-7*((*(! '(! 0.A-05&*A3E! &$*! ,-(&! 7$%33*./'./! -2! %33! A*6*3-),*.&%3! *.'/,%(8! F!
7-,5'.%&'-.! -2! /*.*&'7C! 7*3303%+C! %.A! -+/%.'(,%3! %))+-%7$*(! '(! /'6'./! 0(! %! )+*3','.%+E!
0.A*+(&%.A'./!-2!$-4!&$*!5%('7!%.%&-,E!-2!&$*!5+%'.!5*7-,*(!-+A*+*A8!
B$*!2%&*(!-2!&$*!6*+&*5+%&*!*7&-A*+,!%+*!($-4.!'.!G'/0+*!=?8=8!H.!&$*!)%(&!&4-!7$%)&*+(C!
4*!$%6*!(**.!$-4!&$*!*7&-A*+,! '(! '.(&+07&*A! &-! 2-+,! &$*!.*+6-0(!(E(&*,!%.A! &$*!*)'A*+,'(8!F!
)-+&'-.! -2! &$*! A-+(%3! *7&-A*+,! '(! ()*7'2'*A! &-! 5*7-,*! .*0+%3! *7&-A*+,C! %.A! '&(! 7*33(! 5*7-,*!
A'(&'./0'($%53*! 5E! &$*'+! 7-30,.%+! %))*%+%.7*8! B$'(! +*/'-.! -2! &$*! *,5+E-! '(! 7%33*A! &$*!neural 
plate8!B$*!)+-7*((!5E!4$'7$!&$'(!&'((0*!2-+,(!%!neural tubeC!&$*!+0A',*.&!-2!&$*!7*.&+%3!.*+6-0(!
(E(&*,C! '(! 7%33*A! neurulationC! %.A! %.! *,5+E-! 0.A*+/-'./! (07$! 7$%./*(! '(! 7%33*A! %! neurula!
<G'/0+*!=?8?@8!B$*!.*0+%3! &05*!4'33! 2-+,! &$*!5+%'.! %.&*+'-+3E! %.A!
&$*! ()'.%3!7-+A8!B$'(!7$%)&*+!4'33! 3--D!%&! &$*!)+-7*((*(!5E!4$'7$!
&$*!.*0+%3!&05*!%.A!&$*!*)'A*+,'(!%+'(*!%.A!%710'+*!&$*'+!A'(&'.7&'6*!
)%&&*+.(8!!
!
 
 
 
 
 
 
 
 
 
 
Ectoderme  em  Vertebrados	
A  ectoderme  em  
vertebrados  origina  3  
estruturas:	
A  Placa  Neural  é  uma  estrutura  
externa  do  embrião,  no  entanto  o  
SNC  é  uma  estrutura  interna	
Neurulação  é  o  processo  que  
move  a  placa  neural  para  dentro  
do  embrião,  formando  o  tubo  
neural	
!
"#! $%&!'&()*+!,+*$&!-.! -./+*$&01! -$.!2&++.!2/'3&)4&!*'0!&5$&'0!$/!6*7&!*!$%-''&)!,+*$&1!8($!
#*-+! $/! )/++! (,! -'$/! *!'&()*+! $(8&9!:/;&3&)1! -#! $%&! <8/)0&)! )&4-/'<! 2/'$*-'-'4!8/$%!,)&.(6,$-3&!
&,-0&)6-.!*'0!'&()*+!,+*$&!$-..(&!-.!-./+*$&01!-$!;-++!#/)6!.6*++!'&()*+!#/+0.!-'!2(+$()&!=>*2/8./'!
*'0!?/()@!ABBCD!?/()@!*'0!E2%/&';/+#!ABBCF9!
G-4!AH9I 
Bending of the neural plate.!
J%&!8&'0-'4!/#!$%&!'&()*+!,+*$&!-'3/+3&.!$%&!#/)6*$-/'!/#!hinge regions!;%&)&!$%&!'&()*+!
$(8&!2/'$*2$.!.())/('0-'4!$-..(&.9!"'!$%&.&!)&4-/'.1!$%&!,)&.(6,$-3&!&,-0&)6*+!2&++.!*0%&)&!$/!$%&!
+*$&)*+!&04&.!/#!$%&!'&()*+!,+*$&!*'0!6/3&!$%&6!$/;*)0!$%&!6-0+-'&!=.&&!G-4()&!AH9KLF9!"'!8-)0.!
*'0! 6*66*+.1! $%&! 2&++.! *$! $%&! 6-0+-'&! /#! $%&! '&()*+! ,+*$&! *)&! 2*++&0! $%&! medial hinge point!
=MHPF!cells9!J%&@!*)&!0&)-3&0!#)/6!$%&!,/)$-/'!/#!$%&!'&()*+!,+*$&!M(.$!*'$&)-/)!$/!:&'.&'N.!'/0&!
*'0! #)/6! $%&! *'$&)-/)!6-0+-'&!/#!:&'.&'N.!'/0&! =E2%/&';/+#! ABBA*18D!O*$*+*! &$! *+9! ABBPF9!J%&!
?:Q! 2&++.! 8&2/6&! *'2%/)&0! $/! $%&! '/$/2%/)0! 8&'&*$%! $%&6! *'0! #/)6! *! %-'4&1!;%-2%! #/)6.! *!
#())/;!*$!$%&!0/).*+!6-0+-'&9!J%&!'/$/2%/)0!-'0(2&.!$%&!?:Q!2&++.!$/!0&2)&*.&!$%&-)!%&-4%$!*'0!$/!
8&2/6&!;&04&R.%*,&0!=3*'!E$)**$&'!&$!*+9!ABSSD!E6-$%!*'0!E2%/&';/+#!ABSBF9!J%&!2&++.!+*$&)*+!$/!
$%&!?:Q!0/!'/$! ('0&)4/! .(2%! *! 2%*'4&! =G-4()&.!AH9KL1OF9!E%/)$+@! $%&)&*#$&)1! $;/!/$%&)!%-'4&!
)&4-/'.!#/)6!#())/;.!'&*)!$%&!2/''&2$-/'!/#!$%&!'&()*+!,+*$&!;-$%!$%&!)&6*-'0&)!/#!$%&!&2$/0&)69!
J%&.&!)&4-/'.!*)&!2*++&0! $%&!dorsolateral hinge points! =DLHPsF1!*'0! $%&@!*)&!*'2%/)&0! $/! $%&!
.()#*2&!&2$/0&)6!/#!$%&!'&()*+!#/+0.9!J%&.&!2&++.1! $//1! -'2)&*.&!$%&-)!%&-4%$!*'0!8&2/6&!;&04&R
.%*,&09!
Neurulação  em  diferentes  ângulos	
Formação  do  Tubo  Neural	
Neurulação  Primária	
1)   Extensão  da  Placa  Neural:  divisões  
celulares   no   sentido   antero-­‐‑
posterior	
2)  Curvatura  da  Placa  Neural:  regiões  
de   curvatura   são   formadas   e   a   região  
central   do   tubo   neural   adere-­‐‑se   à  
notocorda	
4)   Fechamento   do   tubo   neural:   as  
duas  pregas  neurais  unem-­‐‑se  	
3)  Aproximação  das  pregas  neurais	
Noggin  bloqueia  BMPs	
Sonic  hedgehog  bloqueia  Noggin	
Ausência  de  BMPs  permite  a  mudança  de  
conformação  das  células	
Fechamento  do  Tubo  Neural	
Não  ocorre  simultaneamente  em  todo  ectoderma	
Região  anterior  mais  adiantada  que  a  caudal	
Fechamento  do  Tubo  Neural	
Em  galinhas  o  tubo  neural  fecha-­‐‑se  como  um  zíper  a  partir  do  encéfalo  médio	
Em  mamíferos,  o  fechamento  inicia-­‐‑se  em  vários  pontos  simultâneamente	
Embrião  de  
camundongo	
Neuroporo  
anterior	
Neuroporo  
posterior	
Fechamento  do  Tubo  Neural	
Em  alguns  pontos  o  fechamento  do  tubo  neural  parece  depender  de  
prolongamentos  celulares  do  ectoderma  não  neuronal	
Fechamento  do  Tubo  Neural	
A  expressão  diferencial  de  caderinas  garante  que  o  tubo  neural  se  separe  do  
ectoderma	
Injeção  de  E-­‐‑caderina  em  
metade  do  embrião	
Fechamento  do  Tubo  Neural	
 Problemas	
Em  cada  1000  nascidos  vivos,  1  apresenta  problemas  no  fechamento  do  tubo  neural	
Espinha  bífida  oculta	
ü Causas:  Fatores  ambientais,  nutricionais  e  
certas  drogas  (anticonvulsivantes)	
ü Prevenção  com  vitaminas  e  ácido  fólico	
Arcos  
vertebrais  não  
fusionados	
Espinha  Bífida  =  Problema  de  extensão  variável  no  sítio  de  fechamento  5  	
Fechamento  do  Tubo  Neural	
Problemas	
Espinha  bífida  cística	
Medula  espinhal  deslocada	
 Medula  espinhal  aberta	
Meningomielocele	
 Mielosquise:  neuroporo  caudal  permanece  
aberto	
Fechamento  do  Tubo  Neural	
Problemas	
Anencefalia  =  Porção  anterior  do  tubo  neural  não  se  fecha,  problema  nos  sítios  2  e  3	
Cranioraquidise  =  Problema  no  fechamento  de  todo  o  tubo  neural	
Fechamento  do  Tubo  Neural	
 Problemas	
!
"#$!%&'(!
)*+,-! -.*/,0! 1*2.! 3045*/.! /.6*#/.5! ,! 34+70.8! #-1./70,9! 2.1:..-! $.-.1#3! ,-;!
.-<#/4-+.-1,0!=,314/5'!>./1,#-!$.-.5?!5*3@!,5!Pax3,sonic hedgehog,!,-;!openbrain,!,/.!.55.-1#,0!
=4/!1@.!=4/+,1#4-!4=!1@.!+,++,0#,-!-.*/,0!1*2.?!2*1!;#.1,/9!=,314/5?!5*3@!,5!3@40.51./40!,-;!=40#3!
,3#;?!,054!,77.,/!14!2.!3/#1#3,0'!A1!@,5!2..-!.51#+,1.;!1@,1!BCD!4=!@*+,-!-.*/,0!1*2.!;.=.315!34*0;!
2.!7/.<.-1.;!29!,!7/.$-,-1!:4+,-E5! 1,F#-$!5*770.+.-1,0! =40#3!,3#;!G<#1,+#-!H%&I?!,-;! 1@.!J'K'!
L*20#3!).,01@!K./<#3.!/.34++.-;5!1@,1!,00!:4+.-!4=!3@#0;2.,/#-$!,$.!1,F.!C'M!+$!4=!=40,1.!;,#09!
14! /.;*3.! 1@.! /#5F! 4=! -.*/,0! 1*2.! ;.=.315! ;*/#-$! 7/.$-,-39! GN#0*-5F9! .1! ,0'! %OPOQ!>R.#R.0! ,-;!
S*;,5!%OO&Q!>.-1./5!=4/!S#5.,5.!>4-1/40!%OO&I'!
T@.! -.*/,0! 1*2.! .<.-1*,009! =4/+5! ,! 3045.;! 390#-;./! 1@,1! 5.7,/,1.5! =/4+! 1@.! 5*/=,3.!
.314;./+'!T@#5!5.7,/,1#4-!#5!1@4*$@1!14!2.!+.;#,1.;!29!1@.!.87/.55#4-!4=!;#==./.-1!3.00!,;@.5#4-!
+40.3*0.5'!U01@4*$@!1@.!3.005!1@,1!:#00!2.34+.!1@.!-.*/,0!1*2.!4/#$#-,009!.87/.55!VW3,;@./#-?!1@.9!
5147!7/4;*3#-$! 1@#5!7/41.#-!,5! 1@.!-.*/,0! 1*2.! =4/+5?!,-;! #-51.,;!59-1@.5#R.!XW3,;@./#-!,-;!XW
>UN!G"#$*/.!%&'YI'!U5!,!/.5*01?!1@.!5*/=,3.!.314;./+!,-;!-.*/,0!1*2.!1#55*.5!-4!04-$./!,;@./.!14!
.,3@!41@./'!A=!1@.!5*/=,3.!.314;./+!#5!.87./#+.-1,009!+,;.!14!.87/.55!XW3,;@./#-!G29!#-Z.31#-$!XW
3,;@./#-!+[XU!#-14!4-.!3.00!4=!,!&W3.00!Xenopus!.+2/94I?!1@.!5.7,/,1#4-!4=!1@.!-.*/,0!1*2.!=/4+!
1@.!7/.5*+71#<.!.7#;./+#5!#5!;/,+,1#3,009!#+7.;.;!GS.1/#3F!.1!,0'!%OOCQ!"*Z#+4/#!.1!,0'!%OOCI'!!
Secondary neurulation !
K.34-;,/9! -.*/*0,1#4-! #-<40<.5! 1@.! +,F#-$! 4=! ,! medullary cord! ,-;! #15! 5*25.6*.-1!
@4004:#-$! #-14! ,! -.*/,0! 1*2.! G"#$*/.! %&'PI'! \-4:0.;$.! 4=! 1@.! +.3@,-#5+5! 4=! 5.34-;,/9!
-.*/*0,1#4-!+,9!2.!#+74/1,-1! #-!+.;#3#-.?!$#<.-!1@.!7/.<,0.-3.!4=!@*+,-!7451./#4/!57#-,0!34/;!
+,0=4/+,1#4-5'!!
Fechamento  do  Tubo  Neural	
Causas  do  não  fechamento	
Fatores  Genéticos:	
Mutação  nos  genes  Pax3,  Sonic  hedgehog,  Grainyhead,  AP-­‐‑2  e  Openbrain	
Fatores  Ambientais:	
Colesterol:	
Atuaria  como  cofator  na  via  de  sinalização  Sonic  hedghog	
Ácido  Fólico:	
-­‐‑Modo  de  atuação  desconhecido,  possível  regulador  da  duplicação  do  DNA  
cerebral	
-­‐‑Metade  dos  casos  de  não  fechamento  do  tubo  neural  podem  ser  evitados  com  
suplementação  de  ácido  fólico	
Neurulação  Secundária	
Tubo  neural  formado  a  partir  de  mesênquima	
Responsável  pela  formação  da  porção  posterior  do  tubo  neural	
Aves:	
Tubo  neural  a  partir  dos  membros  posteriores	
Mamíferos:	
Porção  sacral  do  tubo  neural	
Anfíbios  e  Peixes:	
Tubo  neural  da  cauda	
!
"#! $%&'(! )#*! +,-+.(/! (0+&#*)%1! #02%23)4-&#! -(! 2(2)331! (00#! -#!
4,0!#02%)3!4250!&$!4,0!3265)%!7)5*&6-#)38!)#*!4)-3!90%405%)0:!"#!
5&4,!+)(0(/! -4!+)#!50!(00#!)(!)!+&#4-#2)4-&#!&$!')(4%23)4-&#:!"#!
4,0!$%&'/!-#(40)*!&$!-#9&324-#'!-#4&!4,0!065%1&/!4,0!+033(!&$!4,0!
*&%()3!53)(4&;&%0!3-;!.00;!'%&<-#'!90#4%)331!7=-'2%0!>?:@A/!B8:!
C,0! '%&<-#'! %0'-&#! )4! 4,0! 4-;! &$! 4,0! 3-;! -(! +)330*! 4,0!
chordoneural hinge! 7D)(4003(! >@EF8/! )#*! -4! +&#4)-#(! ;%0+2%(&%(! $&%! 5&4,! 4,0! ;&(40%-&%6&(4!
;&%4-&#!&$!4,0!#02%)3!;3)40!)#*!4,0!;&(40%-&%!;&%4-&#!&$!4,0!#&4&+,&%*:!C,0!'%&<4,!&$!4,-(!%0'-&#!
+&#90%4(! 4,0! %&2',31! (;,0%-+)3! ')(4%23)/! >:?!66! -#! *-)6040%/! -#4&! )! 3-#0)%! 4)*;&30! (&60! @!66!
3&#':!C,0!4-;!&$!4,0!4)-3!-(!4,0!*-%0+4!*0(+0#*)#4!&$!4,0!*&%()3!53)(4&;&%0!3-;/!)#*!4,0!+033(!3-#-#'!
4,0!53)(4&;&%0!$&%6!4,0!neurenteric canal:!
!
!C,0!;%&G-6)3!;)%4!&$! 4,0!#02%0#40%-+!+)#)3!$2(0(!<-4,!4,0!)#2(/!<,-30!4,0!*-(4)3!;&%4-&#!
50+&60(! 4,0! ependymal canal! 7-:0:/! 4,0! 3260#! &$! 4,0! #02%)3! 42508! 7=-'2%0! >?:@HI! J&#4! 04! )3:!
>@@E8:!!
Differentiation of the Neural Tube!
C,0! *-$$0%0#4-)4-&#! &$! 4,0! #02%)3! 4250! -#4&! 4,0! 9)%-&2(! %0'-&#(! &$! 4,0! +0#4%)3! #0%9&2(!
(1(406!&++2%(!(-6234)#0&2(31! -#! 4,%00!*-$$0%0#4!<)1(:!K#!4,0!'%&((!)#)4&6-+)3! 30903/! 4,0!#02%)3!
4250!)#*!-4(!3260#!523'0!)#*!+&#(4%-+4!4&!$&%6!4,0!+,)650%(!&$!4,0!5%)-#!)#*!4,0!(;-#)3!+&%*:!A4!
4,0! 4-((20! 30903/! 4,0!+033!;&;23)4-&#(!<-4,-#! 4,0!<)33!&$! 4,0!#02%)3! 4250! %0)%%)#'0! 4,06(0390(! 4&!
$&%6! 4,0! *-$$0%0#4! $2#+4-&#)3! %0'-&#(! &$! 4,0! 5%)-#! )#*! 4,0! (;-#)3! +&%*:! =-#)331/! &#! 4,0! +03323)%!
30903/! 4,0! #02%&0;-4,03-)3! +033(! 4,06(0390(! *-$$0%0#4-)40! -#4&! 4,0! #260%&2(! 41;0(! &$! #0%90! +033(!
7neurons8!)#*!(2;;&%4-90!+033(!7glia8!;%0(0#4!-#!4,0!5&*1:!
C,0!0)%31!*0903&;60#4!&$!6&(4!90%405%)40!5%)-#(!-(!(-6-3)%/!524!50+)2(0!4,0!,26)#!5%)-#!
6)1!50!4,0!6&(4!&%')#-L0*!;-0+0!&$!6)440%!-#!4,0!(&3)%!(1(406!)#*!-(!)%'2)531!4,0!6&(4!-#40%0(4-#'!
&%')#!-#!4,0!)#-6)3!.-#'*&6/!<0!<-33!+&#+0#4%)40!&#!4,0!*0903&;60#4!4,)4!-(!(2;;&(0*!4&!6).0!
Homo!();-0#4:!
 !"#! $%&'(! )#*! +,-+.(/! (0+&#*)%1! #02%23)4-&#! -(! 2(2)331! (00#! -#!
4,0!#02%)3!4250!&$!4,0!3265)%!7)5*&6-#)38!)#*!4)-3!90%405%)0:!"#!
5&4,!+)(0(/! -4!+)#!50!(00#!)(!)!+&#4-#2)4-&#!&$!')(4%23)4-&#:!"#!
4,0!$%&'/!-#(40)*!&$!-#9&324-#'!-#4&!4,0!065%1&/!4,0!+033(!&$!4,0!
*&%()3!53)(4&;&%0!3-;!.00;!'%&<-#'!90#4%)331!7=-'2%0!>?:@A/!B8:!
C,0! '%&<-#'! %0'-&#! )4! 4,0! 4-;! &$! 4,0! 3-;! -(! +)330*! 4,0!
chordoneural hinge! 7D)(4003(! >@EF8/! )#*! -4! +&#4)-#(! ;%0+2%(&%(! $&%! 5&4,! 4,0! ;&(40%-&%6&(4!
;&%4-&#!&$!4,0!#02%)3!;3)40!)#*!4,0!;&(40%-&%!;&%4-&#!&$!4,0!#&4&+,&%*:!C,0!'%&<4,!&$!4,-(!%0'-&#!
+&#90%4(! 4,0! %&2',31! (;,0%-+)3! ')(4%23)/! >:?!66! -#! *-)6040%/! -#4&! )! 3-#0)%! 4)*;&30! (&60! @!66!
3&#':!C,0!4-;!&$!4,0!4)-3!-(!4,0!*-%0+4!*0(+0#*)#4!&$!4,0!*&%()3!53)(4&;&%0!3-;/!)#*!4,0!+033(!3-#-#'!
4,0!53)(4&;&%0!$&%6!4,0!neurenteric canal:!
!
!C,0!;%&G-6)3!;)%4!&$! 4,0!#02%0#40%-+!+)#)3!$2(0(!<-4,!4,0!)#2(/!<,-30!4,0!*-(4)3!;&%4-&#!
50+&60(! 4,0! ependymal canal! 7-:0:/! 4,0! 3260#! &$! 4,0! #02%)3! 42508! 7=-'2%0! >?:@HI! J&#4! 04! )3:!
>@@E8:!!
Differentiation of the Neural Tube!
C,0! *-$$0%0#4-)4-&#! &$! 4,0! #02%)3! 4250! -#4&! 4,0! 9)%-&2(! %0'-&#(! &$! 4,0! +0#4%)3! #0%9&2(!
(1(406!&++2%(!(-6234)#0&2(31! -#! 4,%00!*-$$0%0#4!<)1(:!K#!4,0!'%&((!)#)4&6-+)3! 30903/! 4,0!#02%)3!
4250!)#*!-4(!3260#!523'0!)#*!+&#(4%-+4!4&!$&%6!4,0!+,)650%(!&$!4,0!5%)-#!)#*!4,0!(;-#)3!+&%*:!A4!
4,0! 4-((20! 30903/! 4,0!+033!;&;23)4-&#(!<-4,-#! 4,0!<)33!&$! 4,0!#02%)3! 4250! %0)%%)#'0! 4,06(0390(! 4&!
$&%6! 4,0! *-$$0%0#4! $2#+4-&#)3! %0'-&#(! &$! 4,0! 5%)-#! )#*! 4,0! (;-#)3! +&%*:! =-#)331/! &#! 4,0! +03323)%!
30903/! 4,0! #02%&0;-4,03-)3! +033(! 4,06(0390(! *-$$0%0#4-)40! -#4&! 4,0! #260%&2(! 41;0(! &$! #0%90! +033(!
7neurons8!)#*!(2;;&%4-90!+033(!7glia8!;%0(0#4!-#!4,0!5&*1:!
C,0!0)%31!*0903&;60#4!&$!6&(4!90%405%)40!5%)-#(!-(!(-6-3)%/!524!50+)2(0!4,0!,26)#!5%)-#!
6)1!50!4,0!6&(4!&%')#-L0*!;-0+0!&$!6)440%!-#!4,0!(&3)%!(1(406!)#*!-(!)%'2)531!4,0!6&(4!-#40%0(4-#'!
&%')#!-#!4,0!)#-6)3!.-#'*&6/!<0!<-33!+&#+0#4%)40!&#!4,0!*0903&;60#4!4,)4!-(!(2;;&(0*!4&!6).0!
Homo!();-0#4:!
 
!
"#! $%&'(! )#*! +,-+.(/! (0+&#*)%1! #02%23)4-&#! -(! 2(2)331! (00#! -#!
4,0!#02%)3!4250!&$!4,0!3265)%!7)5*&6-#)38!)#*!4)-3!90%405%)0:!"#!
5&4,!+)(0(/! -4!+)#!50!(00#!)(!)!+&#4-#2)4-&#!&$!')(4%23)4-&#:!"#!
4,0!$%&'/!-#(40)*!&$!-#9&324-#'!-#4&!4,0!065%1&/!4,0!+033(!&$!4,0!
*&%()3!53)(4&;&%0!3-;!.00;!'%&<-#'!90#4%)331!7=-'2%0!>?:@A/!B8:!
C,0! '%&<-#'! %0'-&#! )4! 4,0! 4-;! &$! 4,0! 3-;! -(! +)330*! 4,0!
chordoneural hinge! 7D)(4003(! >@EF8/! )#*! -4! +&#4)-#(! ;%0+2%(&%(! $&%! 5&4,! 4,0! ;&(40%-&%6&(4!
;&%4-&#!&$!4,0!#02%)3!;3)40!)#*!4,0!;&(40%-&%!;&%4-&#!&$!4,0!#&4&+,&%*:!C,0!'%&<4,!&$!4,-(!%0'-&#!
+&#90%4(! 4,0! %&2',31! (;,0%-+)3! ')(4%23)/! >:?!66! -#! *-)6040%/! -#4&! )! 3-#0)%! 4)*;&30! (&60! @!66!
3&#':!C,0!4-;!&$!4,0!4)-3!-(!4,0!*-%0+4!*0(+0#*)#4!&$!4,0!*&%()3!53)(4&;&%0!3-;/!)#*!4,0!+033(!3-#-#'!
4,0!53)(4&;&%0!$&%6!4,0!neurenteric canal:!
!
!C,0!;%&G-6)3!;)%4!&$! 4,0!#02%0#40%-+!+)#)3!$2(0(!<-4,!4,0!)#2(/!<,-30!4,0!*-(4)3!;&%4-&#!
50+&60(! 4,0! ependymal canal! 7-:0:/! 4,0! 3260#! &$! 4,0! #02%)3! 42508! 7=-'2%0! >?:@HI! J&#4! 04! )3:!
>@@E8:!!
Differentiation of the Neural Tube!
C,0! *-$$0%0#4-)4-&#! &$! 4,0! #02%)3! 4250! -#4&! 4,0! 9)%-&2(! %0'-&#(! &$! 4,0! +0#4%)3! #0%9&2(!
(1(406!&++2%(!(-6234)#0&2(31! -#! 4,%00!*-$$0%0#4!<)1(:!K#!4,0!'%&((!)#)4&6-+)3! 30903/! 4,0!#02%)3!
4250!)#*!-4(!3260#!523'0!)#*!+&#(4%-+4!4&!$&%6!4,0!+,)650%(!&$!4,0!5%)-#!)#*!4,0!(;-#)3!+&%*:!A4!
4,0! 4-((20! 30903/! 4,0!+033!;&;23)4-&#(!<-4,-#! 4,0!<)33!&$! 4,0!#02%)3! 4250! %0)%%)#'0! 4,06(0390(! 4&!
$&%6! 4,0! *-$$0%0#4! $2#+4-&#)3! %0'-&#(! &$! 4,0! 5%)-#! )#*! 4,0! (;-#)3! +&%*:! =-#)331/! &#! 4,0! +03323)%!
30903/! 4,0! #02%&0;-4,03-)3! +033(! 4,06(0390(! *-$$0%0#4-)40! -#4&! 4,0! #260%&2(! 41;0(! &$! #0%90! +033(!
7neurons8!)#*!(2;;&%4-90!+033(!7glia8!;%0(0#4!-#!4,0!5&*1:!
C,0!0)%31!*0903&;60#4!&$!6&(4!90%405%)40!5%)-#(!-(!(-6-3)%/!524!50+)2(0!4,0!,26)#!5%)-#!
6)1!50!4,0!6&(4!&%')#-L0*!;-0+0!&$!6)440%!-#!4,0!(&3)%!(1(406!)#*!-(!)%'2)531!4,0!6&(4!-#40%0(4-#'!
&%')#!-#!4,0!)#-6)3!.-#'*&6/!<0!<-33!+&#+0#4%)40!&#!4,0!*0903&;60#4!4,)4!-(!(2;;&(0*!4&!6).0!
Homo!();-0#4:!
 
Neurulação  Secundária	
A,B)  Formação  de  um  cordão  
medular    abaixo  do  ectoderme	
C)  Cavitação  do  cordão  e  
formação  da  notocorda	
D)  União  em  um  único  lúmen	
Células  da  linha  primitiva  na  porção  posterior  do  embrião  possuem  células  
capazes  de  originar  tanto  mesênquima  quanto  neuroectoderme	
Sox2  –  originarão  tubo  neural	
Tbx6  –  originarão  mesoderma  paraxial  (Tbx6  inibe  Sox2)	
Construção  do  Cérebro	
O  maior  dos  enigmas  da  Biologia  do  Desenvolvimento	
Anatomicamente:	
Surgimento  de  constrições  e  protuberâncias  formando  os  ventrículos  cerebrais  e  a  
medula  nervosa	
Histologicamente:	
As  células  se  organizam  em  regiões  especializadas  do  cérebro	
Biologia  Celular:	
As  células  do  neuroectoderme  se  diferenciam  em  diferentes  tipos  celulares:  
neurônios  e  células  da  glia	
Eixo  Antero-­‐‑Posterior	
!
12. The central nervous system and the epidermis 
"#$%&! '(! )*+$%)(! &$*! ,-(&! '.&+'/0'./! 10*(&'-.! -2! %33! '(! 4$*&$*+! &$*! 5+%'.! '(! )-4*+203!
*.-0/$!&-!(-36*! &$*!)+-53*,!-2! '&(!-4.!7+*%&'-.8"!9-!:+*/-+!;'7$*3*! <=>>?@!*.A*A!%! +*6'*4!-2!
+*(*%+7$!-.!,%,,%3'%.!5+%'.!A*6*3-),*.&8!B$*!7-.(&+07&'-.!-2!%.!-+/%.!&$%&!)*+7*'6*(C!&$'.D(C!
3-6*(C! $%&*(C! +*,*,5*+(C! 7$%./*(C! 2--3(! '&(*32C! %.A! 7--+A'.%&*(! -0+! 7-.(7'-0(! %.A! 0.7-.(7'-0(!
5-A'3E! )+-7*((*(! '(! 0.A-05&*A3E! &$*! ,-(&! 7$%33*./'./! -2! %33! A*6*3-),*.&%3! *.'/,%(8! F!
7-,5'.%&'-.! -2! /*.*&'7C! 7*3303%+C! %.A! -+/%.'(,%3! %))+-%7$*(! '(! /'6'./! 0(! %! )+*3','.%+E!
0.A*+(&%.A'./!-2!$-4!&$*!5%('7!%.%&-,E!-2!&$*!5+%'.!5*7-,*(!-+A*+*A8!
B$*!2%&*(!-2!&$*!6*+&*5+%&*!*7&-A*+,!%+*!($-4.!'.!G'/0+*!=?8=8!H.!&$*!)%(&!&4-!7$%)&*+(C!
4*!$%6*!(**.!$-4!&$*!*7&-A*+,! '(! '.(&+07&*A! &-! 2-+,! &$*!.*+6-0(!(E(&*,!%.A! &$*!*)'A*+,'(8!F!
)-+&'-.! -2! &$*! A-+(%3! *7&-A*+,! '(! ()*7'2'*A! &-! 5*7-,*! .*0+%3! *7&-A*+,C! %.A! '&(! 7*33(! 5*7-,*!
A'(&'./0'($%53*! 5E! &$*'+! 7-30,.%+! %))*%+%.7*8! B$'(! +*/'-.! -2! &$*! *,5+E-! '(! 7%33*A! &$*!neural 
plate8!B$*!)+-7*((!5E!4$'7$!&$'(!&'((0*!2-+,(!%!neural tubeC!&$*!+0A',*.&!-2!&$*!7*.&+%3!.*+6-0(!
(E(&*,C! '(! 7%33*A! neurulationC! %.A! %.! *,5+E-! 0.A*+/-'./! (07$! 7$%./*(! '(! 7%33*A! %! neurula!
<G'/0+*!=?8?@8!B$*!.*0+%3! &05*!4'33! 2-+,! &$*!5+%'.! %.&*+'-+3E! %.A!
&$*! ()'.%3!7-+A8!B$'(!7$%)&*+!4'33! 3--D!%&! &$*!)+-7*((*(!5E!4$'7$!
&$*!.*0+%3!&05*!%.A!&$*!*)'A*+,'(!%+'(*!%.A!%710'+*!&$*'+!A'(&'.7&'6*!
)%&&*+.(8!!
!
 
 
 
 
 
 
 
 
 
 
!
The anterior-posterior axis!
"#$!$%&'(!)%))%'*%+!+$,&%'!-,.$!*/!%!/-&%*0#-!/-&,1-,&$2!345$6$&7!$6$+!.$84&$!-#$!
94/-$&*4&!94&-*4+!48!-#$!-,.$!#%/!84&)$:7!-#$!)4/-!%+-$&*4&!94&-*4+!48!-#$!-,.$!*/!,+:$&04*+0!
:&%/-*1!1#%+0$/2!;+!-#*/!&$0*4+7!-#$!+$,&%'!-,.$!.%''44+/!*+-4!-#&$$!9&*)%&(!6$/*1'$/!<=*0,&$!>?2>@AB!
84&$.&%*+!<prosencephalonA7!)*:.&%*+!<mesencephalonA7!
%+:!#*+:.&%*+!<rhombencephalonA2!
!C(!-#$!-*)$!-#$!94/-$&*4&!$+:!48!-#$!+$,&%'!-,.$!1'4/$/7!/$14+:%&(!.,'0$/ -#$!optic 
vesicles #%6$!$D-$+:$:!'%-$&%''(!8&4)!$%1#!/*:$!48!-#$!:$6$'49*+0!84&$.&%*+2!!
"#$!9&4/$+1$9#%'4+!.$14)$/! /,.:*6*:$:! *+-4! -#$! %+-$&*4&! telencephalon! %+:! -#$!)4&$!
1%,:%'!diencephalon2!"#$!-$'$+1$9#%'4+!5*''!$6$+-,%''(!84&)!-#$!1$&$.&%'!#$)*/9#$&$/7!%+:!-#$!
:*$+1$9#%'4+! 5*''! 84&)! -#$! -#%'%)*1! %+:! #(94-#%'%)*1! .&%*+! &$0*4+/! -#%-! &$1$*6$! +$,&%'! *+9,-!
8&4)!-#$!&$-*+%2!;+:$$:7!-#$!&$-*+%!*-/$'8!*/!%!:$&*6%-*6$!48!-#$!:*$+1$9#%'4+2!"#$!)$/$+1$9#%'4+!
:4$/! +4-! .$14)$! /,.:*6*:$:7! %+:! *-/! ',)$+! $6$+-,%''(! .$14)$/! -#$! 1$&$.&%'! %E,$:,1-2! "#$!
&#4).$+1$9#%'4+! .$14)$/! /,.:*6*:$:! *+-4! %! 94/-$&*4&! myelencephalon! %+:! %! )4&$! %+-$&*4&!
metencephalon2!"#$!)($'$+1$9#%'4+!$6$+-,%''(!.$14)$/!-#$!)$:,''%!4.'4+0%-%7!5#4/$!+$,&4+/!0$+$&%-$!-#$!+$&6$/!-#%-!&$0,'%-$!&$/9*&%-4&(7!0%/-&4*+-$/-*+%'7!%+:!1%&:*46%/1,'%&!)46$)$+-/2!"#$!
)$-$+1$9#%'4+! 0*6$/! &*/$! -4! -#$! 1$&$.$'',)7! -#$! 9%&-! 48! -#$! .&%*+! &$/94+/*.'$! 84&! 144&:*+%-*+0!
)46$)$+-/7! 94/-,&$7! %+:! .%'%+1$2! "#$! &#4).$+1$9#%'4+! :$6$'49/! %! /$0)$+-%'! 9%--$&+! -#%-!
/9$1*8*$/! -#$! 9'%1$/! 5#$&$! 1$&-%*+! +$&6$/! 4&*0*+%-$2! F$&*4:*1! /5$''*+0/! 1%''$:! rhombomeres!
:*6*:$! -#$!&#4).$+1$9#%'4+! *+-4!/)%''$&!14)9%&-)$+-/2!"#$/$!&#4).4)$&$/! &$9&$/$+-!/$9%&%-$!
:$6$'49)$+-%'!G-$&&*-4&*$/G!*+!-#%-!-#$!1$''/!5*-#*+!$%1#!&#4).4)$&$!1%+!)*D!8&$$'(!5*-#*+!*-7!.,-!
+4-!5*-#!1$''/!8&4)!%:H%1$+-!&#4).4)$&$/!<I,-#&*$!%+:!J,)/:$+!>KK>A2!!! !!!!!!!!!!
L4&$46$&7! $%1#! &#4).4)$&$! #%/! %! :*88$&$+-! :$6$'49)$+-%'! 8%-$2! M%1#! &#4).4)$&$! 5*''! 84&)!
ganglia 1',/-$&/! 48! +$,&4+%'! 1$''! .4:*$/! 5#4/$! %D4+/! 84&)! %! +$&6$2!
"#$! 0$+$&%-*4+! 48! -#$! 1&%+*%'! +$&6$/! 8&4)! -#$! &#4).4)$&$/! #%/! .$$+!
)4/-!$D-$+/*6$'(!/-,:*$:!*+!-#$!1#*1N7!*+!5#*1#!-#$!8*&/-!+$,&4+/!%99$%&!
*+! -#$! $6$+O+,).$&$:! &#4).4)$&$/7! &?7! &P7! %+:! &Q! <=*0,&$! >?2>>R!
J,)/:$+!%+:!S$(+$/!>KTKA2!U$,&4+/!4&*0*+%-*+0!8&4)!&?!0%+0'*%!84&)!
-#$! 8*8-#! <-&*0$)*+%'A! 1&%+*%'! +$&6$R! -#4/$! 8&4)! &P! 84&)! -#$! /$6$+-#!
<8%1*%'A! %+:! $*0#-#! <6$/-*.,'4%14,/-*1A! 1&%+*%'! +$&6$/R! %+:! -#$! +*+-#!
<0'4//49#%&(+0$%'A!1&%+*%'!+$&6$!$D*-/!8&4)!&Q2!!
As  estruturas  cerebrais  vão  se  formando  
progressivamente	
Eixo  Antero-­‐‑Posterior	
Diferenciação  entre  Encéfalo  e  Medula  Espinhal	
!
"#$!%&''(()*)+!(,!-#$!$&.'/!$0%./()*1!%.&*)!*2!.$0&.3&%'$!*)!*-2!.&-$4!*)!*-2!$5-$)-4!&)6!*)!
*-2!%$*)+!-#$!.$27'-!8.*0&.*'/!(,!&)!*)1.$&2$!*)!1&9*-/!2*:$4!)(-!-*227$!+.(;-#<!=)!-#$!1#*13!$0%./(4!
%.&*)!9('70$!$58&)62!-#*.-/>,('6!%$-;$$)!6&/2!?!&)6!@!(,!6$9$'(80$)-<!"#*2!.&8*6!$58&)2*()!*2!
-#(7+#-!-(!%$!1&72$6!%/!8(2*-*9$!,'7*6!8.$227.$!$5$.-$6!&+&*)2-!-#$!;&''2!(,!-#$!)$7.&'!-7%$!%/!-#$!
,'7*6!;*-#*)!*-<!=-!0*+#-!%$!$58$1-$6!-#&-!-#*2!,'7*6!8.$227.$!;(7'6!%$!6*22*8&-$6!%/!-#$!28*)&'!1(.64!
%7-! -#*2!6($2!)(-! &88$&.! -(!#&88$)<!A&-#$.4! &2! -#$!)$7.&'! ,('62!1'(2$! *)! -#$! .$+*()!%$-;$$)! -#$!
8.$2708-*9$! %.&*)! &)6! -#$! 8.$2708-*9$! 28*)&'! 1(.64! -#$! 27..(7)6*)+! 6(.2&'! -*227$2! 872#! *)! -(!
1()2-.*1-!-#$!)$7.&'!-7%$!&-!-#$!%&2$!(,!-#$!%.&*)!BC*+7.$!DE<DEF!G1#($);(',!&)6!H$20()6!DIJKF!
H$20()6!&)6!G1#($);(',!DIJLF!H$20()6!&)6!C*$'6!DIIEM<!"#*2!(11'72*()!B;#*1#!&'2(!(117.2!*)!
-#$!#70&)!$0%./(M!$,,$1-*9$'/!2$8&.&-$2!-#$!8.$2708-*9$!%.&*)!.$+*()!,.(0!-#$!,7-7.$!28*)&'!1(.6!
BH$20()6! DIJEM<! =,! -#$! ,'7*6! 8.$227.$! *)! -#$! &)-$.*(.!
8(.-*()! (,! 271#! &)! (11'76$6! )$7.&'! -7%$! *2!
$58$.*0$)-&''/!.$0(9$64!-#$!1#*13!%.&*)!$)'&.+$2!&-!&!
071#!2'(;$.!.&-$!&)6!1()-&*)2!0&)/!,$;$.!1$''2! -#&)!
&.$!,(7)6!*)!)(.0&'!$0%./(2<!"#$!(11'76$6!.$+*()!(,!
-#$! )$7.&'! -7%$! .$(8$)2! &,-$.! -#$! *)*-*&'! .&8*6!
$)'&.+$0$)-!(,!-#$!%.&*)!9$)-.*1'$2<!!
!
 
 
 
The dorsal-ventral axis!
"#$!)$7.&'!-7%$!*2!8('&.*:$6!&'()+!*-2!6(.2&'>9$)-.&'!
&5*2<!=)!-#$!28*)&'!1(.64!,(.!*)2-&)1$4!-#$!dorsal!.$+*()!*2!-#$!
8'&1$!;#$.$! -#$!28*)&'!)$7.()2! .$1$*9$! *)87-! ,.(0!2$)2(./!
)$7.()24! ;#*'$! -#$! ventral! .$+*()! *2! ;#$.$! -#$! 0(-(.!
)$7.()2! .$2*6$<! =)! -#$! 0*66'$! &.$! )70$.(72! *)-$.)$7.()2!
-#&-! .$'&/! *),(.0&-*()! %$-;$$)! -#$0<! "#$! 8('&.*-/! (,! -#$!
)$7.&'! -7%$! *2! *)671$6! %/! 2*+)&'2! 1(0*)+! ,.(0! *-2!
*00$6*&-$! $)9*.()0$)-<! "#$! 6(.2&'! 8&--$.)! *2! *08(2$6! %/!
-#$! $8*6$.0*24! ;#*'$! -#$! 9$)-.&'! 8&--$.)! *2! *)671$6! %/! -#$!
)(-(1#(.6!BC*+7.$!DE<D?M<!!
 
Obliteração  da  luz  no  limite  
entre  as  duas  estruturas	
Crescimento  acelerado  
do  encéfalo	
Reestabelecimento  da  
comunicação  	
Eixo  Dorso-­‐‑Ventral	
!
"#$!%&''(()*)+!(,!-#$!$&.'/!$0%./()*1!%.&*)!*2!.$0&.3&%'$!*)!*-2!.&-$4!*)!*-2!$5-$)-4!&)6!*)!
*-2!%$*)+!-#$!.$27'-!8.*0&.*'/!(,!&)!*)1.$&2$!*)!1&9*-/!2*:$4!)(-!-*227$!+.(;-#<!=)!-#$!1#*13!$0%./(4!
%.&*)!9('70$!$58&)62!-#*.-/>,('6!%$-;$$)!6&/2!?!&)6!@!(,!6$9$'(80$)-<!"#*2!.&8*6!$58&)2*()!*2!
-#(7+#-!-(!%$!1&72$6!%/!8(2*-*9$!,'7*6!8.$227.$!$5$.-$6!&+&*)2-!-#$!;&''2!(,!-#$!)$7.&'!-7%$!%/!-#$!
,'7*6!;*-#*)!*-<!=-!0*+#-!%$!$58$1-$6!-#&-!-#*2!,'7*6!8.$227.$!;(7'6!%$!6*22*8&-$6!%/!-#$!28*)&'!1(.64!
%7-! -#*2!6($2!)(-! &88$&.! -(!#&88$)<!A&-#$.4! &2! -#$!)$7.&'! ,('62!1'(2$! *)! -#$! .$+*()!%$-;$$)! -#$!
8.$2708-*9$! %.&*)! &)6! -#$! 8.$2708-*9$! 28*)&'! 1(.64! -#$! 27..(7)6*)+! 6(.2&'! -*227$2! 872#! *)! -(!
1()2-.*1-!-#$!)$7.&'!-7%$!&-!-#$!%&2$!(,!-#$!%.&*)!BC*+7.$!DE<DEF!G1#($);(',!&)6!H$20()6!DIJKF!
H$20()6!&)6!G1#($);(',!DIJLF!H$20()6!&)6!C*$'6!DIIEM<!"#*2!(11'72*()!B;#*1#!&'2(!(117.2!*)!
-#$!#70&)!$0%./(M!$,,$1-*9$'/!2$8&.&-$2!-#$!8.$2708-*9$!%.&*)!.$+*()!,.(0!-#$!,7-7.$!28*)&'!1(.6!
BH$20()6! DIJEM<! =,! -#$! ,'7*6! 8.$227.$! *)! -#$! &)-$.*(.!
8(.-*()! (,! 271#! &)! (11'76$6! )$7.&'! -7%$! *2!
$58$.*0$)-&''/!.$0(9$64!-#$!1#*13!%.&*)!$)'&.+$2!&-!&!
071#!2'(;$.!.&-$!&)6!1()-&*)2!0&)/!,$;$.!1$''2! -#&)!
&.$!,(7)6!*)!)(.0&'!$0%./(2<!"#$!(11'76$6!.$+*()!(,!
-#$! )$7.&'! -7%$! .$(8$)2! &,-$.! -#$! *)*-*&'! .&8*6!
$)'&.+$0$)-!(,!-#$!%.&*)!9$)-.*1'$2<!!
!
 
 
 
The dorsal-ventral axis!
"#$!)$7.&'!-7%$!*2!8('&.*:$6!&'()+!*-2!6(.2&'>9$)-.&'!
&5*2<!=)!-#$!28*)&'!1(.64!,(.!*)2-&)1$4!-#$!dorsal!.$+*()!*2!-#$!
8'&1$!;#$.$! -#$!28*)&'!)$7.()2! .$1$*9$! *)87-! ,.(0!2$)2(./!
)$7.()24! ;#*'$! -#$! ventral! .$+*()! *2! ;#$.$! -#$! 0(-(.!
)$7.()2! .$2*6$<! =)! -#$! 0*66'$! &.$! )70$.(72! *)-$.)$7.()2!
-#&-! .$'&/! *),(.0&-*()! %$-;$$)! -#$0<! "#$! 8('&.*-/! (,! -#$!
)$7.&'! -7%$! *2! *)671$6! %/! 2*+)&'2! 1(0*)+! ,.(0! *-2!
*00$6*&-$! $)9*.()0$)-<! "#$! 6(.2&'! 8&--$.)! *2! *08(2$6! %/!
-#$! $8*6$.0*24! ;#*'$! -#$! 9$)-.&'! 8&--$.)! *2! *)671$6! %/! -#$!
)(-(1#(.6!BC*+7.$!DE<D?M<!!
 
Ectoderme  estimula  a  diferenciação  de  uma  placa  dorsal  no  tubo  neural	
Notocorda  estimula  a  diferenciação  de  uma  placa  ventral  no  tubo  neural	
Eixo  Dorso-­‐‑Ventral	
!
"#$!%&''(()*)+!(,!-#$!$&.'/!$0%./()*1!%.&*)!*2!.$0&.3&%'$!*)!*-2!.&-$4!*)!*-2!$5-$)-4!&)6!*)!
*-2!%$*)+!-#$!.$27'-!8.*0&.*'/!(,!&)!*)1.$&2$!*)!1&9*-/!2*:$4!)(-!-*227$!+.(;-#<!=)!-#$!1#*13!$0%./(4!
%.&*)!9('70$!$58&)62!-#*.-/>,('6!%$-;$$)!6&/2!?!&)6!@!(,!6$9$'(80$)-<!"#*2!.&8*6!$58&)2*()!*2!
-#(7+#-!-(!%$!1&72$6!%/!8(2*-*9$!,'7*6!8.$227.$!$5$.-$6!&+&*)2-!-#$!;&''2!(,!-#$!)$7.&'!-7%$!%/!-#$!
,'7*6!;*-#*)!*-<!=-!0*+#-!%$!$58$1-$6!-#&-!-#*2!,'7*6!8.$227.$!;(7'6!%$!6*22*8&-$6!%/!-#$!28*)&'!1(.64!
%7-! -#*2!6($2!)(-! &88$&.! -(!#&88$)<!A&-#$.4! &2! -#$!)$7.&'! ,('62!1'(2$! *)! -#$! .$+*()!%$-;$$)! -#$!
8.$2708-*9$! %.&*)! &)6! -#$! 8.$2708-*9$! 28*)&'! 1(.64! -#$! 27..(7)6*)+! 6(.2&'! -*227$2! 872#! *)! -(!
1()2-.*1-!-#$!)$7.&'!-7%$!&-!-#$!%&2$!(,!-#$!%.&*)!BC*+7.$!DE<DEF!G1#($);(',!&)6!H$20()6!DIJKF!
H$20()6!&)6!G1#($);(',!DIJLF!H$20()6!&)6!C*$'6!DIIEM<!"#*2!(11'72*()!B;#*1#!&'2(!(117.2!*)!
-#$!#70&)!$0%./(M!$,,$1-*9$'/!2$8&.&-$2!-#$!8.$2708-*9$!%.&*)!.$+*()!,.(0!-#$!,7-7.$!28*)&'!1(.6!
BH$20()6! DIJEM<! =,! -#$! ,'7*6! 8.$227.$! *)! -#$! &)-$.*(.!
8(.-*()! (,! 271#! &)! (11'76$6! )$7.&'! -7%$! *2!
$58$.*0$)-&''/!.$0(9$64!-#$!1#*13!%.&*)!$)'&.+$2!&-!&!
071#!2'(;$.!.&-$!&)6!1()-&*)2!0&)/!,$;$.!1$''2! -#&)!
&.$!,(7)6!*)!)(.0&'!$0%./(2<!"#$!(11'76$6!.$+*()!(,!
-#$! )$7.&'! -7%$! .$(8$)2! &,-$.! -#$! *)*-*&'! .&8*6!
$)'&.+$0$)-!(,!-#$!%.&*)!9$)-.*1'$2<!!
!
 
 
 
The dorsal-ventral axis!
"#$!)$7.&'!-7%$!*2!8('&.*:$6!&'()+!*-2!6(.2&'>9$)-.&'!
&5*2<!=)!-#$!28*)&'!1(.64!,(.!*)2-&)1$4!-#$!dorsal!.$+*()!*2!-#$!
8'&1$!;#$.$! -#$!28*)&'!)$7.()2! .$1$*9$! *)87-! ,.(0!2$)2(./!
)$7.()24! ;#*'$! -#$! ventral! .$+*()! *2! ;#$.$! -#$! 0(-(.!
)$7.()2! .$2*6$<! =)! -#$! 0*66'$! &.$! )70$.(72! *)-$.)$7.()2!
-#&-! .$'&/! *),(.0&-*()! %$-;$$)! -#$0<! "#$! 8('&.*-/! (,! -#$!
)$7.&'! -7%$! *2! *)671$6! %/! 2*+)&'2! 1(0*)+! ,.(0! *-2!
*00$6*&-$! $)9*.()0$)-<! "#$! 6(.2&'! 8&--$.)! *2! *08(2$6! %/!
-#$! $8*6$.0*24! ;#*'$! -#$! 9$)-.&'! 8&--$.)! *2! *)671$6! %/! -#$!
)(-(1#(.6!BC*+7.$!DE<D?M<!!Sonic  hedgehog	
dorsalin	
Neurônios  motores	
!
Ventral patterning of the neural tube.!
"#$!%&$'()('*+(,-!,)! +#$!.$-+/*0!-$1/*0! +12$!*&&$*/%! +,!2$!3$4(*+$4!25!$6+$/-*0! +(%%1$%7!
8-$!*9$-+!,)!.$-+/*0!%&$'()('*+(,-!(%!+#$!Sonic hedgehog!&/,+$(-:!&/,2*205!,/(9(-*+(-9!)/,3!+#$!
-,+,'#,/4;!*-,+#$/!*9$-+!%&$'()5(-9!+#$!.$-+/*0!-$1/*0!'$00!+5&$%!(%!/$+(-,('!*'(4:!<#('#!&/,2*205!
',3$%!)/,3!+#$!*4=*'$-+!%,3(+$%!>?($/*-(!$+!*07!@AAAB7!C,-('!#$49$#,9!$%+*20(%#$%!*!9/*4($-+:!*-4!
4())$/$-+! 0$.$0%! ,)! +#(%! &/,+$(-! '*1%$! +#$! ),/3*+(,-! ,)! 4())$/$-+! '$00! +5&$%7! C,-('! #$49$#,9! (%!
(-(+(*005!%5-+#$%(D$4!(-!+#$!-,+,'#,/47!E$/$!(+!(%!&/,'$%%$4!25!'#,0$%+$/,0F3$4(*+$4!'0$*.*9$:!*-4!
+#$!*'+(.$!),/3!,)! +#$!&/,+$(-!>+#$!*3(-,F+$/3(-*0!&,/+(,-B! (%!%$'/$+$4!)/,3!+#$!-,+,'#,/47!"#$!
%$'/$+$4!C,-('!#$49$#,9!(-41'$%!+#$!3$4(*0!#(-9$!'$00%!+,!2$',3$!+#$!floor plate!,)!+#$!-$1/*0!
+12$7!"#$%$!)0,,/!&0*+$!'$00%!*0%,!%$'/$+$!C,-('!#$49$#,9:!<#('#!),/3%!*!9/*4($-+!#(9#$%+!*+! +#$!
3,%+! .$-+/*0! &,/+(,-! ,)! +#$! -$1/*0! +12$! >G,$0(-H! $+! *07! @AAI;!J/(%',$! $+! *07! @AAAB7! "#,%$! '$00%!
*4=*'$-+!+,!+#$!)0,,/!&0*+$!+#*+!/$'$(.$!#(9#!',-'$-+/*+(,-%!,)!C,-('!#$49$#,9!2$',3$!+#$!.$-+/*0!
>KLB! -$1/,-%:!<#(0$! +#$! -$6+! 9/,1&! ,)! '$00%:! $6&,%$4! +,! %0(9#+05! 0$%%! C,-('! #$49$#,9:! 2$',3$!
3,+,/!-$1/,-%!>M(91/$!@N7@OB7!"#$!-$6+!+<,!9/,1&%!,)!'$00%:!/$'$(.(-9!&/,9/$%%(.$05!0$%%!,)!+#(%!
&/,+$(-:! 2$',3$! +#$! KN! *-4!K@! (-+$/-$1/,-%7! "#$! 4())$/$-+! ',-'$-+/*+(,-%! ,)! C,-('! #$49$#,9!
)1-'+(,-! 25! '*1%(-9! +#$! 4())$/$-+! 9/,1&%! ,)! -$1/,-%! +,! $6&/$%%! 4())$/$-+! +5&$%! ,)! +/*-%'/(&+(,-!
)*'+,/%7!"#$%$! +/*-%'/(&+(,-! )*'+,/%:! (-! +1/-:! *'+(.*+$! +#$! 9$-$%!<#,%$!&/,+$(-!&/,41'+%! 9(.$! +#$!
'$00!(+%!(4$-+(+57!C,-('!#$49$#,9!3*5!*0%,!<,/H!25!/$&/$%%(-9!+#$!$6&/$%%(,-!,)!9$-$%!$-',4(-9!
4,/%*0!-$1/*0!+12$!+/*-%'/(&+(,-!)*'+,/%7!"#$%$!9$-$%!<,104!,+#$/<(%$!2$!$6&/$%%$4!+#/,19#,1+!+#$!
-$1/*0!+12$7!!
"#$!(3&,/+*-'$!,)!C,-('!#$49$#,9!(-!(-41'(-9!*-4!&*++$/-(-9!+#$!.$-+/*0!&,/+(,-!,)!+#$!
-$1/*0!+12$!'*-!2$!%#,<-!$6&$/(3$-+*0057!P)!-,+,'#,/4!)/*93$-+%!*/$!+*H$-!)/,3!,-$!$32/5,!*-4!
+/*-%&0*-+$4!+,!+#$!0*+$/*0!%(4$!,)!*!#,%+!-$1/*0!+12$:!+#$!#,%+!-$1/*0!+12$!<(00!),/3!*-,+#$/!%$+!,)!
)0,,/! &0*+$! '$00%! *+! (+%! %(4$%! >M(91/$! @N7@OJB7! "#$! )0,,/! &0*+$! '$00%:! ,-'$! (-41'$4:! (-41'$! +#$!
),/3*+(,-! ,)! 3,+,/! -$1/,-%! ,-! $(+#$/! %(4$! ,)! +#$37! "#$! %*3$! /$%10+%! '*-! 2$! ,2+*(-$4! ()! +#$!
-,+,'#,/4!)/*93$-+%!*/$!/$&0*'$4!25!&$00$+%!,)!'10+1/$4!'$00%!%$'/$+(-9!C,-('!#$49$#,9!>Q'#$0*/4!
$+!*07!@AAL;!G,$0(-H!$+!*07!@AAOB7!R,/$,.$/:!()!*!&($'$!,)!-,+,'#,/4!(%!/$3,.$4!)/,3!*-!$32/5,:!
+#$!-$1/*0!+12$!*4=*'$-+!+,!+#$!4$0$+$4!/$9(,-!<(00!#*.$!-,!)0,,/!&0*+$!'$00%!>?0*'D$H!$+!*07!@AAS;!
T*3*4*!$+!*07!@AA@:!@AALB7!!
Dorsal patterning of the neural tube.!
"#$!4,/%*0!)*+$%!,)!+#$!-$1/*0!+12$!*/$!$%+*20(%#$4!25!&/,+$(-%!,)!+#$!"UMFȕ!%1&$/)*3(05:!
$%&$'(*005! +#$! 2,-$! 3,/&#,9$-$+('! &/,+$(-%! O! *-4! V:! 4,/%*0(-:! *-4! *'+(.(-! >W($3! $+! *07! @AAI:!
@AAVB7!P-(+(*005:!JR?O!*-4!JR?V!*/$!),1-4!(-!+#$!$&(4$/3(%7!!
Eixo  Dorso-­‐‑Ventral	
Diferenciação  dos  Neurônios  no  Cérebro	
Células  neuroepiteliais  do  tubo  neural  devem  originar  três  linhagens  celulares:	
1)  Células  ventriculares/ependimárias	
Diferenciação  dos  Neurônios  no  Cérebro	
Células  neuroepiteliais  do  tubo  neural  devem  originar  três  linhagens  celulares:	
1)  Células  ventriculares/ependimárias	
2)  Precursores  dos  neurônios	
Diferenciação  dos  Neurônios  no  Cérebro	
Células  neuroepiteliais  do  tubo  neural  devem  originar  três  linhagens  celulares:	
1)  Células  ventriculares/ependimárias	
2)  Precursores  dos  neurônios	
3)  Células  da  Glia	
Crescimento  do  Axônio	
Ross  Harrison,  1907...	
Crescimento  do  Axônio	
Como  o  axônio  encontra  seu  caminho?	
Cone  de  Crescimento	
Diferenciação  Neuronal	
FGF  e  Sonic  hedgehog