ΠΠΎΠ²ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Noggin: ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² Activin/Nodal ΠΈ Wnt Π² ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ
ΠΠ΄Π½ΠΎΠΉ ΠΈΠ· Π²Π°ΠΆΠ½Π΅ΠΉΡΠΈΡ Π·Π°Π΄Π°Ρ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΠΎΠΈΡΠΊ ΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ°ΠΊΡΠΎΡΠΎΠ², ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠΈΡ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΎΠ½Π½ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ ΡΠΊΠ°Π½Π΅ΠΉ Π² Ρ ΠΎΠ΄Π΅ ΡΠΌΠ±ΡΠΈΠΎΠ³Π΅Π½Π΅Π·Π°. Π‘Π΅ΠΊΡΠ΅ΡΠΈΡΡΠ΅ΠΌΡΠΉ Π±Π΅Π»ΠΎΠΊ Noggin (Nogginl) ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΠ΅ΡΠ²ΡΠΌ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ Π±Π΅Π»ΠΊΠΎΠ²ΡΠΌ ΡΠ°ΠΊΡΠΎΡΠΎΠΌ, ΡΡΠ°ΡΡΠ²ΡΡΡΠΈΠΌ Π² ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ. ΠΠ½ Π±ΡΠ» ΠΎΡΠΊΡΡΡ Π ΠΈΡΠ°ΡΠ΄ΠΎΠΌ Π₯Π°ΡΠ»Π°Π½Π΄ΠΎΠΌ Π² 1992 Π³. Ρ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ Xenopus ΠΊΠ°ΠΊ Π½Π΅ΠΉΡΠ°Π»ΡΠ½ΡΠΉ… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- 1. ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅
- 2. ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
- 2. 1. ΠΠ±ΡΠΈΠ΅ ΠΏΡΠΈΠ½ΡΠΈΠΏΡ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ. ΠΠ΅ΠΉΡΠ°Π»ΡΠ½Π°Ρ ΠΈΠ½Π΄ΡΠΊΡΠΈΡ
- 2. 2. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄ TGF-P
- 2. 2. 1. Π‘ΡΠΏΠ΅ΡΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²ΠΎ TGF-J
- 2. 2. 2. ΠΠ°ΡΠΊΠ°Π΄ Activin/Nodal
- 2. 2. 3. ΠΠ½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ Activin-ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 2. 2. 4. Π Π΅ΡΠ΅ΠΏΡΠΎΡΡ Activin
- 2. 2. 5. Π Π΅Π³ΡΠ»ΡΡΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² Activin
- 2. 2. 6. Π Π΅Π³ΡΠ»ΡΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π° Activin ΡΠ΅ΡΠ΅Π· Π±Π΅Π»ΠΊΠΈ Smad
- 2. 2. 7. ΠΠ΅Π½Ρ-ΠΌΠΈΡΠ΅Π½ΠΈ Smad2 ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 2. 2. 8. Smad-Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΏΡΡΡ Activin ΠΈ ΠΏΠ΅ΡΠ΅ΠΊΡΠ΅ΡΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ²
- 2. 2. 9. Π ΠΎΠ»Ρ Activin ΠΈ TGF-|3 Π² ΠΊΠ°Π½ΡΠ΅ΡΠΎΠ³Π΅Π½Π΅Π·Π΅
- 2. 2. 10. Activin ΠΈ ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ
- 2. 2. 11. ΠΠ°ΡΠΊΠ°Π΄ BMP
- 2. 2. 12. Π€ΡΠ½ΠΊΡΠΈΠΈ BMP
- 2. 2. 13. ΠΠ½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΠΠΠ -ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 2. 2. 14. ΠΠ½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΠΠΠ -ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 2. 2. 15. ΠΠ΅Π½Ρ-ΠΌΠΈΡΠ΅Π½ΠΈ Smadl- (BMP-) ΠΊΠ°ΡΠΊΠ°Π΄Π°
- 2. 3. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΊΠ°ΡΠΊΠ°Π΄ Wnt
- 2. 3. 1. ΠΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ Wnt Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ²
- 2. 3. 2. ΠΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΡΡΡ Wnt (Wnt/(3-Catenin)
- 2. 3. 3. ΠΠ»Π°Π½Π°ΡΠ½Π°Ρ ΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ ΠΏΠΎΠ»ΡΡΠ½ΠΎΡΡΡ (PCP)
- 2. 3. 4. ΠΠ΅ΠΊΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ Wnt/Ca2+ ΠΏΡΡΡ
- 2. 3. 5. Π‘Π΅ΠΊΡΠ΅ΡΠΈΡ Wnt ΠΈ Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΡ
- 2. 3. 6. Wnt-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΠΎΡΠ²Π΅ΡΡ
- 2. 4. ΠΠ²ΠΎΠ»ΡΡΠΈΠΎΠ½Π½ΠΎΠ΅ ΠΏΡΠΎΠΈΡΡ ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² TGF-(3 ΠΈ Wnt
- 2. 5. ΠΠ·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² Π² ΡΠ°Π½Π½Π΅ΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Xenopus
- 2. 6. Π Π΅Π³ΠΈΠΎΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΡ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΡΡΠ±ΠΊΠΈ Π² Ρ ΠΎΠ΄Π΅ ΡΠΌΠ±ΡΠΈΠΎΠ³Π΅Π½Π΅Π·Π°
- 2. 7. Π‘Π΅ΠΌΠ΅ΠΉΡΡΠ²ΠΎ Π±Π΅Π»ΠΊΠΎΠ² Noggin
- 2. 7. 1. Π€ΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½Π°Ρ ΡΠΎΠ»Ρ Noggin
- 2. 7. 2. Π‘ΡΡΡΠΊΡΡΡΠ° Noggin
- 2. 7. 3. Noggin ΠΊΠ°ΠΊ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡ BMP
- 2. 7. 4. ΠΠ΅Π»ΠΎΠΊ Noggin ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° (HNoggin)
- 2. 7. 5. ΠΡΡΠ°ΡΠΈΠΈ Π³Π΅Π½Π° Noggin
- 3. 1. ΠΠ»ΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ Π½ΠΎΠ²ΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Noggin
- 3. 2. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½ΠΎΠ² Noggin Π² ΡΠ°Π½Π½Π΅ΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ
- 3. 3. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΎΠ² ΡΠΊΡΠΎΠΏΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½ΠΎΠ² Nogginl ΠΈ -2 Π² ΡΠ°Π½Π½Π΅ΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ
- 3. 4. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΈ ΠΌΠ ΠΠ Π³Π΅Π½ΠΎΠ² Nogginl ΠΈ -2 Π² ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Ρ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ
- 3. 5. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π»ΠΈΠ³Π°Π½Π΄-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² Π±Π΅Π»ΠΊΠΎΠ² Nogginl ΠΈ
- 3. 6. Nogginl ΠΈ Noggin2 ΡΠΏΠΎΡΠΎΠ±Π½Ρ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Activin/Nodal- ΠΈ Wnt-ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² Π² ΠΆΠΈΠ²ΡΡ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Ρ
- 3. 7. Nogginl ΠΈ Noggin2 ΡΠΏΠΎΡΠΎΠ±Π½Ρ Π²Π»ΠΈΡΡΡ Π½Π° ΠΎΠ½ΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ΅ΡΡΡ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΠ΅ΠΌΡΠ΅ Activin/Nodal- ΠΈ Wnt- ΠΊΠ°ΡΠΊΠ°Π΄Π°ΠΌΠΈ Π² ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Ρ
- 3. 8. ΠΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Noggin2, Π½ΠΎ Π½Π΅ Nogginl, Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠ° Π΄Π»Ρ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ Xenopus
- 3. 9. ΠΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Activin-ΠΊΠ°ΡΠΊΠ°Π΄Π° ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ Noggin2 Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎ Π΄Π»Ρ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΏΠ΅ΡΠ΅Π΄Π½Π΅ΠΌΠΎΠ·Π³ΠΎΠ²ΡΡ ΡΡΡΡΠΊΡΡΡ
- 4. 1. TGF-p Π»ΠΈΠ³Π°Π½Π΄Ρ (ΠΏΠΎΠΌΠΈΠΌΠΎ BMP) ΠΈ Wnt ΡΠ²Π»ΡΡΡΡΡ ΠΌΠΈΡΠ΅Π½ΡΠΌΠΈ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Noggin
- 4. 2. ΠΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Activin-, BMP- ΠΈ Wnt-ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ Noggin2 Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎ Π΄Π»Ρ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΏΠ΅ΡΠ΅Π΄Π½Π΅ΠΌΠΎΠ·Π³ΠΎΠ²ΡΡ ΡΡΡΡΠΊΡΡΡ
- 6. 1. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ
- 6. 1. 1. Π Π΅Π°ΠΊΡΠΈΠ²Ρ
- 6. 1. 2. Π€Π΅ΡΠΌΠ΅Π½ΡΠ½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ
- 6. 1. 3. ΠΠ°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΠΎΠ΅ ΠΎΠ±ΠΎΡΡΠ΄ΠΎΠ²Π°Π½ΠΈΠ΅
- 6. 1. 4. ΠΠ°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΠ΅ ΠΆΠΈΠ²ΠΎΡΠ½ΡΠ΅
- 6. 1. 5. ΠΡΡΠ΅ΡΡ ΠΈ ΡΠ°ΡΡΠ²ΠΎΡΡ
- 6. 1. 6. ΠΠΈΠΊΡΠΎΠ±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ΅Π΄Ρ
- 6. 1. 7. ΠΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½Π½ΡΠ΅ ΡΡΠ°ΠΌΠΌΡ
- 6. 1. 8. ΠΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½Π½ΡΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ
- 6. 2. ΠΠ΅ΡΠΎΠ΄Ρ
- 6. 2. 1. ΠΠΌΠΏΠ»ΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΠΠ ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ (ΠΠ¦Π )
- 6. 2. 2. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² Π°Π³Π°ΡΠΎΠ·Π½ΠΎΠΌ Π³Π΅Π»Π΅
- 6. 2. 3. ΠΠ»ΡΡΠΈΡ ΠΠΠ ΠΈΠ· Π°Π³Π°ΡΠΎΠ·Π½ΠΎΠ³ΠΎ Π³Π΅Π»Ρ
- 6. 2. 4. Π Π°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΠ΅ ΠΠΠ ΡΠ½Π΄ΠΎΠ½ΡΠΊΠ»Π΅Π°Π·Π°ΠΌΠΈ ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΈ
- 6. 2. 5. ΠΠΎΡΡΡΠΎΠΉΠΊΠ° 3"-ΠΊΠΎΠ½ΡΠ° Π΄Π²ΡΡ ΡΠ΅ΠΏΠΎΡΠ΅ΡΠ½ΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ» ΠΠΠ
- 6. 2. 6. ΠΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΠ΅ Π²ΡΡΡΡΠΏΠ°ΡΡΠ΅Π³ΠΎ 3″ - ΠΊΠΎΠ½ΡΠ° Π΄Π²ΡΡ ΡΠ΅ΠΏΠΎΡΠ΅ΡΠ½ΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ» ΠΠΠ
- 6. 2. 7. ΠΠΈΠ³ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ» ΠΠΠ
- 6. 2. 8. Π’ΡΠ°Π½ΡΡΠΎΡΠΌΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ Escherichia col
- 6. 2. 9. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ ΠΈΠ· Π±Π°ΠΊΡΠ΅ΡΠΈΠΉ Escherichia col
- 6. 2. 10. ΠΠ·Π³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΡΡ ΠΠΠ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ
- 6. 2. 11. Π’ΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ in vitro
- 6. 2. 12. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ Π·Π°ΡΠΎΠ΄ΡΡΠ΅ΠΉ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ Xenopus laevis
- 6. 2. 13. Π‘ΠΈΠ½ΡΠ΅Π· Π±Π΅Π»ΠΊΠΎΠ² Π² ΠΎΠΎΡΠΈΡΠ°Ρ ΠΈΠ»ΠΈ Π·Π°ΡΠΎΠ΄ΡΡΠ°Ρ Xenopus laevis
- 6. 2. 14. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ°Π·Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ² Π² Π΄Π΅Π½Π°ΡΡΡΠΈΡΡΡΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΡΡ Π² ΠΠΠΠ
- 6. 2. 15. ΠΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡ (Western Blotting)
- 6. 2. 16. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΎΠΊ-Π±Π΅Π»ΠΊΠΎΠ²ΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ Π² ΡΠΈΡΡΠ΅ΠΌΠ΅ in vivo Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΊΠΎΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠ΅ΡΠΈΠΏΠΈΡΠ°ΡΠΈΠΈ
- 6. 2. 17. ΠΠ»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΡΡ ΠΌΠ ΠΠ ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΠΌΠΈΠΊΡΠΎΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΉ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°Π½ΡΠΈΡΠΌΡΡΠ»ΠΎΠ²ΡΡ ΠΎΠ»ΠΈΠ³ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄ΠΎΠ²
- 6. 2. 18. Π€ΠΈΠΊΡΠ°ΡΠΈΡ Π·Π°ΡΠΎΠ΄ΡΡΠ΅ΠΉ
- 6. 2. 19. ΠΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΡ in situ Π½Π° ΡΠ΅Π»ΡΡ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Ρ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ
- 6. 2. 20. Π‘ΠΈΠ½ΡΠ΅Π· Π΄ΠΈΠ³ΠΎΠΊΡΠΈΠ³Π΅Π½ΠΈΠ½-ΠΌΠ΅ΡΠ΅Π½Π½ΠΎΠΉ Π°Π½ΡΠΈΡΠΌΡΡΠ»ΠΎΠ²ΠΎΠΉ Π ΠΠ Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π³ΠΈΠ±ΡΠΈΠ΄ΠΈΠ·Π°ΡΠΈΠΈ in situ
- 6. 2. 21. ΠΠΊΡΡΡΠ°ΠΊΡΠΈΡ ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΉ Π ΠΠ ΠΈΠ· Π·Π°ΡΠΎΠ΄ΡΡΠ΅ΠΉ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ
- 6. 2. 22. ΠΠ±ΡΠ°ΡΠ½Π°Ρ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ ΠΈ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½Π°Ρ ΡΠ΅ΠΏΠ½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ (ΠΠ’-ΠΠ¦Π )
- 6. 2. 23. ΠΠ±ΡΠ°ΡΠ½Π°Ρ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ ΠΈ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½Π°Ρ ΡΠ΅ΠΏΠ½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ (ΠΠ’-ΠΠ¦Π ) Π² ΡΠ΅Π°Π»ΡΠ½ΠΎΠΌ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ
- 6. 2. 24. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ΅ΠΏΠΎΡΡΠ΅ΡΠΎΠ²
ΠΠΎΠ²ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Noggin: ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠ² Activin/Nodal ΠΈ Wnt Π² ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
ΠΠ΄Π½ΠΎΠΉ ΠΈΠ· Π²Π°ΠΆΠ½Π΅ΠΉΡΠΈΡ Π·Π°Π΄Π°Ρ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΠΎΠΈΡΠΊ ΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ°ΠΊΡΠΎΡΠΎΠ², ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠΈΡ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΎΠ½Π½ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ ΡΠΊΠ°Π½Π΅ΠΉ Π² Ρ ΠΎΠ΄Π΅ ΡΠΌΠ±ΡΠΈΠΎΠ³Π΅Π½Π΅Π·Π°. Π‘Π΅ΠΊΡΠ΅ΡΠΈΡΡΠ΅ΠΌΡΠΉ Π±Π΅Π»ΠΎΠΊ Noggin (Nogginl) ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΠ΅ΡΠ²ΡΠΌ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ Π±Π΅Π»ΠΊΠΎΠ²ΡΠΌ ΡΠ°ΠΊΡΠΎΡΠΎΠΌ, ΡΡΠ°ΡΡΠ²ΡΡΡΠΈΠΌ Π² ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ. ΠΠ½ Π±ΡΠ» ΠΎΡΠΊΡΡΡ Π ΠΈΡΠ°ΡΠ΄ΠΎΠΌ Π₯Π°ΡΠ»Π°Π½Π΄ΠΎΠΌ Π² 1992 Π³. Ρ ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ Xenopus ΠΊΠ°ΠΊ Π½Π΅ΠΉΡΠ°Π»ΡΠ½ΡΠΉ ΠΈΠ½Π΄ΡΠΊΡΠΎΡ, ΠΏΡΠΎΠ΄ΡΡΠΈΡΡΠ΅ΠΌΡΠΉ ΡΠΏΠ΅ΠΌΠ°Π½ΠΎΠ²ΡΠΊΠΈΠΌ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΎΡΠΎΠΌ. Nogginl ΡΠΏΠΎΡΠΎΠ±Π΅Π½ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡ Π±Π΅Π»ΠΊΠΈ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· ΡΡΠ±Π³ΡΡΠΏΠΏ ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ² TGF-(3, Π° ΠΈΠΌΠ΅Π½Π½ΠΎ Bone Morphogenetic Proteins (BMP) (Smith and Harland, 1992). ΠΠ΅ΠΉΡΡΠ²ΡΡ Π²Π½Π΅ ΠΊΠ»Π΅ΡΠΊΠΈ, BMP ΠΈΠ½Π΄ΡΡΠΈΡΡΠ΅Ρ Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΡΠ΅ΡΠΈΠ½-ΡΡΠ΅ΠΎΠ½ΠΈΠ½ΠΎΠ²ΡΡ ΠΊΠΈΠ½Π°Π· I ΠΈ II ΡΠΈΠΏΠ°, ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΌΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Smadl/5/8, ΠΊΠΎΡΠΎΡΡΠ΅ Π² ΠΏΠ°ΡΠ΅ ΡΠΎ Smad4 ΠΌΠΈΠ³ΡΠΈΡΡΡΡ Π² ΡΠ΄ΡΠΎ ΠΈ ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΡ ΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ Π³Π΅Π½ΠΎΠ²-ΠΌΠΈΡΠ΅Π½Π΅ΠΉ (Shi and Massague, 2003). Π’Π°ΠΊ ΠΊΠ°ΠΊ Noggin ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΡΠ΅Ρ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ BMP Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ (Groppe et al., 2002), ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΡΠΈ, ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Smadl/5/8. ΠΠ»Π°Π³ΠΎΠ΄Π°ΡΡ ΡΡΠΎΠΉ ΡΡΠ½ΠΊΡΠΈΠΈ, Nogginl, Π±ΡΠ΄ΡΡΠΈ ΡΠΊΡΠΎΠΏΠΈΡΠ΅ΡΠΊΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ Π² Π²Π΅Π½ΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΡΠ°ΡΡΠΈ ΡΠΌΠ±ΡΠΈΠΎΠ½Π° Xenopus, ΡΠΏΠΎΡΠΎΠ±Π΅Π½ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ Π²ΡΠΎΡΠΈΡΠ½ΡΠ΅ ΠΎΡΠΈ, Π»ΠΈΡΠ΅Π½Π½ΡΠ΅ Π³ΠΎΠ»ΠΎΠ². Π Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΌ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Nogginl ΠΈΠ³ΡΠ°Π΅Ρ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΠΏΡΠΎΡΠ΅ΡΡΠ°Ρ , Π²ΠΊΠ»ΡΡΠ°Ρ ΠΈΠ½Π΄ΡΠΊΡΠΈΡ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΈ ΡΠΊΠ΅Π»Π΅ΡΠ½ΠΎΠΉ ΠΌΡΡΠΊΡΠ»Π°ΡΡΡΡ Π² ΡΠ°Π½Π½Π΅ΠΌ ΡΠΌΠ±ΡΠΈΠΎΠ³Π΅Π½Π΅Π·Π΅ (Smith and Harland, 1992), ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ Ρ ΡΡΡΠ΅ΠΉ (Botchkarev et al., 1999) ΠΈ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΡ Π²ΠΎΠ»ΠΎΡΡΠ½ΡΡ ΡΠΎΠ»Π»ΠΈΠΊΡΠ»ΠΎΠ² (Brunei et al., 1998; Botchkarev et al., 1999; Shi and Massague, 2003). ΠΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ ΡΠΈΡΡΠ΅ΠΌΠ°Ρ , Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ, ΠΏΡΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ ΠΈΠ»ΠΈ ΡΠ°ΠΊΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, Nogginl ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΡΡΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΈΡΠΊΡΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° BMP-ΠΊΠ°ΡΠΊΠ°Π΄Π°. Π‘ΡΠΈΡΠ°Π΅ΡΡΡ ΠΎΠ±ΡΠ΅ΠΏΡΠΈΠ·Π½Π°Π½Π½ΡΠΌ, ΡΡΠΎ Nogginl Π½Π΅ ΡΠ²Π»ΡΠ΅ΡΡΡ Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΡΡΠΎΠΌ Π΄Π»Ρ Π΄ΡΡΠ³ΠΎΠΉ ΡΡΠ±Π³ΡΡΠΏΠΏΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² TGF-J3, Activin/Nodal/TGFbeta, ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ ΡΠ΅ΡΠΈΠ½-ΡΡΠ΅ΠΎΠ½ΠΈΠ½ ΠΊΠΈΠ½Π°Π·Π½ΡΠΌΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ ΠΈ ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΡ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ Π΄ΡΡΠ³ΠΎΠ³ΠΎ Π½Π°Π±ΠΎΡΠ° Π³Π΅Π½ΠΎΠ²-ΠΌΠΈΡΠ΅Π½Π΅ΠΉ ΡΠ΅ΡΠ΅Π· Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ Π±Π΅Π»ΠΎΠΊ-ΠΏΠΎΡΡΠ΅Π΄Π½ΠΈΠΊ Smad2/3 (Branford and Yost, 2002). ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠΎΠ³ΠΎ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΡΠΈ Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎ Π΄Π»Ρ ΠΏΡΠ°Π²ΠΈΠ»ΡΠ½ΠΎΠΉ ΡΠ°Π·ΠΌΠ΅ΡΠΊΠΈ ΠΌΠ΅Π·ΠΎΠ΄Π΅ΡΠΌΡ ΠΏΡΠΈ Π³Π°ΡΡΡΡΠ»ΡΡΠΈΠΈ (Piccolo et al., 1999), ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΏΠ΅ΡΠ΅Π΄Π½Π΅Π³ΠΎ ΠΌΠΎΠ·Π³Π° (Meno et al., 2001) ΠΈ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΡ ΠΏΡΠ°Π²ΠΎ-Π»Π΅Π²ΠΎΠΉ Π°ΡΡΠΈΠΌΠΌΠ΅ΡΡΠΈΠΈ (Grande and Patel, 2009).
ΠΠΎΠΌΠΈΠΌΠΎ «ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ» Noggin 1, Ρ ΠΏΠΎΠ·Π²ΠΎΠ½ΠΎΡΠ½ΡΡ Π±ΡΠ»ΠΈ Π½Π°ΠΉΠ΄Π΅Π½Ρ Π΄Π²Π΅ Π΄ΡΡΠ³ΠΈΡ Π³ΡΡΠΏΠΏΡ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Noggin, Noggin2 ΠΈ Noggin4 (Furthauer et al., 1999; Fletcher et al., 2004; Eroshkin et al., 2006). ΠΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΡΠ½ΠΊΡΠΈΡ Π±ΡΠ»Π° ΠΏΠΎΠΊΠ°Π·Π°Π½Π° Π² ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Ρ ΡΠΎΠ»ΡΠΊΠΎ Π΄Π»Ρ Noggin2, ΠΊΠΎΡΠΎΡΡΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΡΠ΅ΡΡΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ Π² Π·Π°ΡΠ°ΡΠΊΠ΅ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΡΠΌΠ±ΡΠΈΠΎΠ½ΠΎΠ² Xenopus ΠΈ Danio. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΡΡΠΈΡ Π΄Π°Π½Π½ΡΡ Π±ΡΠ»ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΎ, ΡΡΠΎ Noggin2 ΠΌΠΎΠΆΠ΅Ρ, ΠΏΠΎ Π±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΠ°ΡΡΠΈ, Π΄ΡΠ±Π»ΠΈΡΠΎΠ²Π°ΡΡ ΠΠΠ -Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΡΡΠΈΡΠ΅ΡΠΊΡΡ ΡΡΠ½ΠΊΡΠΈΡ Nogginl (Furthauer et al., 1999). ΠΠ΄Π½Π°ΠΊΠΎ, ΠΏΠΎ Π½Π°ΡΠ΅ΠΌΡ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ, Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΡ Π² ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΠ΅ Π±Π΅Π»ΠΊΠΎΠ² Noggin, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΏΡΠΈΠ½Π°Π΄Π»Π΅ΠΆΠ°Ρ ΠΊ ΡΠ°Π·Π½ΡΠΌ Π±Π΅Π»ΠΊΠΎΠ²ΡΠΌ ΠΏΠΎΠ΄ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°ΠΌ (Eroshkin et al., 2006), ΠΈ ΡΠ°Π·Π»ΠΈΡΠ°ΡΡΠΈΠ΅ΡΡ ΠΏΠ°ΡΡΠ΅ΡΠ½Ρ ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠΊΠ°Π·ΡΠ²Π°ΡΡ Π½Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΡ Π² ΡΠ΅ΠΏΠ΅ΡΡΡΠ°ΡΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π΅ΠΌΡΡ ΠΈΠΌΠΈ Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°ΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΡΡ ΡΡΠ½ΠΊΡΠΈΡ.
Π ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ, Π·Π°Π΄Π°ΡΠ° Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ — ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π΄Π°Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΠΈΡ ΡΠΎΠ»ΠΈ Π² ΡΠ°Π½Π½Π΅ΠΉ ΡΠΊΠ°Π½Π΅Π²ΠΎΠΉ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΠ΅ — ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π²Π΅ΡΡΠΌΠ° Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ, ΠΊΠ°ΠΊ Ρ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ Π½ΠΎΠ²ΡΡ ΡΡΠ½Π΄Π°ΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ Π·Π½Π°Π½ΠΈΠΉ, ΡΠ°ΠΊ ΠΈ Π²Π²ΠΈΠ΄Ρ Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ Π½ΠΎΠ²ΡΡ Π³Π΅Π½Π½ΠΎ-ΠΈΠ½ΠΆΠ΅Π½Π΅ΡΠ½ΡΡ ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ² Π΄Π»Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠ³ΠΎ ΡΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ ΠΏΡΠΎΡΠ΅ΡΡΠ°ΠΌΠΈ ΠΆΠΈΠ·Π½Π΅Π΄Π΅ΡΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΈ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ.
ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΡ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΡΠΌΠ±ΡΠΈΠΎΠ½ΠΎΠ² ΡΠΏΠΎΡΡΠ΅Π²ΠΎΠΉ Π»ΡΠ³ΡΡΠΊΠΈ Xenopus. ΠΠ°Π½Π½Π°Ρ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΏΡΠΈΠ·Π½Π°Π΅ΡΡΡ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΡ Π΄Π»Ρ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΈ Π² ΡΠ°Π½Π½Π΅ΠΌ ΡΠΌΠ±ΡΠΈΠΎΠ³Π΅Π½Π΅Π·Π΅ ΠΈ, ΠΊΡΠΎΠΌΠ΅ ΡΡΠΎΠ³ΠΎ, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΎΠ±ΠΎΠΉ ΡΠ΄ΠΎΠ±Π½ΡΡ ΡΠ΅ΡΡ-ΡΠΈΡΡΠ΅ΠΌΡ, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΡ ΠΏΡΠΎΡΠ΅ΡΡΡ in vivo.
2. ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ.
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