INTERAKSI SELULER DAN ORGANOGENESIS

1. INTERAKSI SELULER DAN ORGANOGENESIS Ita DJUWITA

2. IDW Sub Pokok Bahasan: • Pengertian organogenesis • Proses & mekanisme pembentukan organ • Interaksi dan diferensiasi seluler • Ekspresi gen & pengaruh lingkungan • Fenotipe, fenokopi, pleiotropism dan letal • Malformasi kongenital dan faktor-faktor • penyebabnya

3. PERKEMBANGAN MAHLUK HIDUP (DEVELOPMENT) IDW Proses secara keseluruhan meng perubahan embrio menjadi fetus – lahir, yg melibatkan a.Pertumbuhan/ Growth (Pembelahan sel) b. Pergerakan & Migrasi Sel (Cell Movement) c. Diferensiasi sel (Cell Differentiation) Ketiga proses berjalan secara overlapping pada saat bersamaan

4. Proses Perkembangan mahluk hidup IDW

6. IDW a. Pertumbuhan, Terjadi penambahan jumlah sel (bahan inti dan sitoplasma) b. Pergerakan sel, Didalam tubuh, jaringan & organ menempati lokasi yg spesifik. Utk mencapai lokasi tsb sel-sel embrio harus bergerak; migrasi dgn cara yg terprogram. c. Diferensiasi sel, Setelah menempati posisi baru, sel akan berdiferensiasi menjadi sel, jaringan atau organ utk menjalankan fungsi ttt berdasark lokasi didalam tubuh

7. I. PENGERTIAN ORGANOGENESIS – MORFOGENESIS IDW Morfogenesis  Perubahan bentuk eksternal Organogenesis Perkembangan organ-organ (the making of organs) • The formation of the products of the neural tube, neural crest cells, the somites, and all of the rest of the cells which develop from the three germinal layers

8. IDW • Organogenesis • is the especially initial formation of organs starting with less differentiated tissues found in the early embryo. • Websters: • "The origin and development of bodily organs."

9. Websters: "The origin and development of bodily organs." Pattern & Calson, 1974

10. II. PROSES & MEKANISME ORGANOGENESIS / MORFOGENESIS IDW 1. Apa yang menginisiasi terjadinya proses organogenesis/ morfogenesis ? 2. Bagaimana proses dan mekanisme organogenesis/ morfogenesis ?

11. 1. INISIASI proses organogenesis Pd Gastrulasi terjadi  perubahan bentuk & pergerakan sel-sel 3 lapis daun kecambah (primary germinal layers) (ektoderm,endoderm, mesoderm, archenteron/ gastrosul) menurunkan jaringan & organ-organ IDW Gastrulasi inisiasi morfogenesis & organogenesis.

12. IDW • Ke-3 daun kecambah akan menurunkan • Empat (4) jaringan utama: • jaringan saraf • jaringan otot • jaringan penghubung • jaringan epitelial There is no one-to-one correspondence between germinal layer origin and primary tissue type.

13. IDW • Endoderm utamanya,jaringanepitelial. • The endoderm secara spesifik menurunkan: saluran digesti • paru-paru • liver • vesika urinaria • germ cells

14. IDW Endoderm

15. Mesoderm jar otot dan penghubung, jaringan epitelial • The mesoderm secara spesifik menurunkan, • skeleton • otot-otot skeletal • tulang kepala dan rahang • mesoderm somit-somit  segmentasi tubuh IDW • which divide bodies into cross sections which may be stacked, for example, from head to toe. • In vertebrates the somites are originally found adjacent to the notochord and then give rise to such things as ribs and skeletal muscles.

16. IDW Earlier in development the mesoderm also gives rise to the epidermis, neural tube, and neural crest, from which these later structures develop

17. IDW 2. MEKANISME proses perkembangan termasuk organogenesis Bagaimana embrio 1 sel (Zigot) dapat berkembang menjadi ORGANISME MULTISELULER? a. Pertumbuhan/ Growth (Pembelahan sel) b. Pergerakan & Migrasi Sel (Cell Movement) c. Diferensiasi sel (Cell Differentiation)

18. IDW b. Migrasi sel: menuju tempat yg spesifik PETA TAKDIR  right place right time POSISI SEL Cell migration The movement of cells which were born in one place to a different place in the embryo or fetus. The addition of new cells of the same type to existing sites.

19. IDW PETA TAKDIR Masing sel memiliki takdir sendiri di tempat akhir TOTIPOTENSI CELL POSITION Migrasi / gerakan Di lokasi akhir akan terjadi induksi dan diferensiasi  Jaringan dan organ-organ tertentu Utk mengemban fungsi tertentu UNIPOTENSI

20. IDW Posisi sel Pada hewan, pergerakan sel / sekelompok sel sangat penting utk mentransformasi embrio kedalam bentuk 3 dimensi  Basic body plan Sumbu tubuh: Kepala - ekor; kiri - kanan; depan - belakang (Body pattern formation) Perkembangan jaringan & organ  tersusun pada tempat yg spesifik.

21. IDW

22. IDW Posisi sel mempengaruhi peta takdir & derivatnya Induksi: mempengaruhi terjadinya diferensiasi e.g., posisi notokorda  induksi ektoderm disebelahnya  membentuk lempeng saraf

23. IDW Contoh: Notokorda Ektoderm Buluh saraf

24. IDW • Programmed cell death / apoptosis: • The removal of cells from existing sites. • Note that very often structures are produced within larger cellular structures, and completion of the structure requires some means of removal of the excess cells. For example, the development of fingers involves the removal of the tissue (webs) initially found between the forming digits. • A variation on right place-right time. Chemical concentration gradients help determine relative position.

25. IDW c. Inisiasi Diferensiasi, diatur oleh • Molekul (mRNA) dr maternal dalam sitoplasma sel embrio akan memicu proses transkripsi dr genom embrio Sitoplasma sel telur mengandung mRNA, protein & bahan-bahan lainnya yg berasal dr maternal  berpengaruh thdp awal perkembangan embrio • Signal yg dikode oleh genom dari sel embrio lainnya akan menginduksi target sel

26. IDW • Differentiation: • The changing of the protein expression pattern of cells in the course of their individual development and division. • Differentiation very often is irreversible. • That is, embryonic cells typically may become more specialized, but similarly typically more specialized (differentiated) cells are not well equipped to become less specialized. Diferensiasi terjadi pd tingkat molekuler krn adanya ekspresi gen utk menghasilkan protein tertentu; misalnya: sel otot  aktin & miosin

27. IDW Lingkungan di sekitar sel mengandung informasi (signal) berupa molekul kimiawi yg dikode oleh gen embrio  molekul dikirim ke sel target sehingga mengakibatkan perubahan pd sel target  proses induksi Induksi terjadi : - difusi molekul signal dan - interaksi permukaan sel

28. III. INTERAKSI dan DIFERENSIASI SEL IDW Interaksi dan induki diferensiasi sel terjadi, melalui: • Difusi substansi: bekerja intraseluler • Hormon, growth factor, morfogen • 2. Interaksi permukaan sel

29. IDW

30. IDW • Struktur membran sel, mengandung : • 1. mol adesi sel • 2. mol adesi substrat • 3. mol junctional sel • 4. mol reseptor • Permukaan membran sel berubah • sejalan waktu dan tempat

31. IDW Contoh model diferensiasi

32. IDW

33. IDW IV. EKSPRESI GEN DAN PENGARUH LINGKUNGAN Diferensiasi dikontrol oleh program genetik & dapat dimodifikasi oleh faktor lingkungan Setiap sel memiliki komplemen penuh, DNA  Dalam organisme, sel-sel yg berbeda memiliki DNA yg sama. Gen tertentu dalam beberapa sel harus ON dan pada sel lainOFF.

34. Bagaimana Gen tertentu dalam beberapa sel harus ON dan pada sel lainOFF Dua faktor utama sel yang mengatur aktivasi gen pada proses perkembangan 1. Bahan Inti / NUCLEUS 2. Bahan SITOPLASMA

35. CELL NUCLEUS CHROMOSOME GENOME/ GENES/ DNA

36. Pengaturan Ekspresi Gen

37. Sel somatis pd mamalia memiliki 2 copy genome (diploid) Kontribusi nyata yg diberikan induk jantan & betina pada anak-anaknya  berbeda-beda Bagaimana gen yang diwariskan dr maternal & paternal berbeda ekspresi ? Terjadi switch off (silencing) pd salah satu copy gen induk Genomic Imprinting

38. IDW

39. Genomic Imprinting, suatu proses EPIGENETIK yg dinamis, yg terlibat dalam pengaturan ekspresi sebagian kecil gen dari genome mamalia melalui proses modifikasi STRUKTUR DNA Memberikan efek terhadap fenotip Pd setiap generasi harus mampu di HAPUS (Off) dan BENTUK (On)

40. Epigenetic reprogramming in germ cells is critical for imprinting, and reprogramming in early embryos also affects imprinting. In germline cells the imprint is erased, and then re-established according to the sex of the individual; i.e. in the developing sperm, a paternal imprint is established, whereas in developing oocytes, a maternal imprint is established. The process of erase and reprogrammingis necessary such that the current imprinting status is relevant to the sex of the individual.

41. Ada 2 mekanisme utama yg terlibat dalam terjadinya imprinting, yakni: 1. Modifikasi Asetilasi Histone 2. Modifikasi Metilasi DNA

42. 1. Asetilasi HISTONE (Aktif transkripsi)

43. Asetilasi residu lisine pd posisi terminus dr protein histonemenghilangkan muatan positif  mengurangi afinitas protein histon ke DNA Enzim polimerase RNA polymerase dan faktor transkripsi lebih mudah berikatan pada promoter Umumnya, asetilasi histon memicu transkripsi; deasetilasi histon menekan transkripsi

44. Acetylation (or ethanoylation): reaction that introduces an acetylfunctional group into an organic compound. Deacetylation is the removal of the acetyl group. Introducing an acetyl group into a compound, the substitution of an acetyl group for an active hydrogen atom. A reaction involving the replacement of the hydrogen atom of a hydroxyl group with an acetyl group (CH3 CO) yields a specific ester, the acetate. Acetic anhydride is commonly used as an acetylating agent reacting with free hydroxyl groups.

45. Acetylation of proteins In biology, i.e. in living cells, acetylation occurs as a post-translational modification of proteins, for example, histones and tubulins. Histone Acetylation and Deacetylation In histone acetylation and deacetylation, the histones are acetylated and deacetylated on lysine residues in the N-terminal tail as part of gene regulation. Typically, these reactions are catalyzed by enzymes with "histone acetyltransferase" (HAt) or "histone deacetylase" (HDAc OR HDs) activity.

46. Several different forms of HATs and HDs have been identified.  Among them, CBP/p300 is probably the most important, since it can interact with numerous transcription regulators.

47. 2. Modifikasi Metilasi DNA Pd embrio preimplantasi terjadi perubahan mayor melalui mekanisme imprinting yakni metilasi DNA Perubahan metilasi DNA diwariskan secara stabil melalui pembelahan sel shg akan tetap sampai tahap fetus.

48. METILASI DNA deaminasi metilasi Penambahan CH3 pada cytosine  Silencing Gene Expression Metilasi residu cytosine  5-methylcytosine Deaminasi 5-methylcytosine  thymine.

49. Pola Metilasi DNA di-program kembali (reprogramming) pada 2 periode perkembangan, yakni: - pada germ cells - pad embrio preimplantation Jika terjadi kerusakan/ gangguan dalam proses atau pemeliharaan imprinting pd masa perkembangan embrio preimplantasi (kultur atau manipulasi embrio), dapat mengakibatkan: - Fetal Loss atau - Large Offspring Syndrome.

50. Methylation is a process that is used to control gene expression, and it is what determines the timing of gene expression  (as in embryologic development, in which genes are turned on and off in a sequential fashion), inactivation of an X-chromosome in a female ("Lyonization"), and, in mammals, differential expression of certain genes depending upon whether they are maternally- or paternally-derived ("genomic imprinting").