INTERAKSI SELULER DAN
ORGANOGENESIS
Ita DJUWITA
Sub Pokok Bahasan:
I.
Pengertian organogenesis
II. Proses & mekanisme pembentukan organ
III. Interaksi dan diferensiasi seluler
IV. Ekspresi gen & pengaruh lingkungan
V. Fenotipe, fenokopi, pleiotropism dan letal
VI. Malformasi kongenital dan faktor-faktor
penyebabnya
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PERKEMBANGAN MAHLUK HIDUP
(DEVELOPMENT)
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
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Proses Perkembangan
mahluk hidup
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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
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I. PENGERTIAN ORGANOGENESIS –
MORFOGENESIS
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
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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."
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Websters: "The origin and development of bodily organs."
Pattern & Calson, 1974
II. PROSES & MEKANISME
ORGANOGENESIS / MORFOGENESIS
1. Apa yang menginisiasi terjadinya proses
organogenesis/ morfogenesis ?
2. Bagaimana proses dan mekanisme
organogenesis/ morfogenesis ?
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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
Gastrulasi  inisiasi morfogenesis &
organogenesis.
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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.
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Endoderm  utamanya, jaringan epitelial.
The endoderm secara spesifik menurunkan:
saluran digesti
paru-paru
liver
vesika urinaria
germ cells
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Endoderm
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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
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.
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Ectoderm  utamanya jaringan saraf
beberapa jaringan epitelial
Secara spesifik  membentuk:
otak
sumsum punggung
sistem saraf tepi
kulit
rambut
mata
Earlier in development the mesoderm also gives
rise to the epidermis, neural tube, and neural
crest, from which these later structures develop
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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)
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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.
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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
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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.
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Posisi sel mempengaruhi peta takdir & derivatnya
Induksi: mempengaruhi terjadinya diferensiasi
e.g., posisi notokorda  induksi ektoderm
disebelahnya  membentuk lempeng saraf
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Contoh:
Notokorda
Ektoderm
Buluh saraf
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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.
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c. Inisiasi Diferensiasi, diatur oleh
1. 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
2. Signal yg dikode oleh genom dari sel embrio
lainnya akan menginduksi target sel
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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 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
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III. INTERAKSI dan DIFERENSIASI SEL
Interaksi dan induki diferensiasi sel terjadi, melalui:
1. Difusi substansi: bekerja intraseluler
Hormon, growth factor, morfogen
2. Interaksi permukaan sel
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• 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
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Contoh model diferensiasi
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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 lain OFF.
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Bagaimana Gen tertentu dalam beberapa
sel harus ON dan pada sel lain OFF
Dua faktor utama sel yang mengatur aktivasi
gen pada proses perkembangan
1. Bahan Inti / NUCLEUS
2. Bahan SITOPLASMA
CELL NUCLEUS
CHROMOSOME
GENOME/ GENES/ DNA
Pengaturan Ekspresi Gen
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
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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)
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 reestablished 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 reprogramming is
necessary such that the current imprinting
status is relevant to the sex of the individual.
Ada 2 mekanisme utama yg terlibat dalam
terjadinya imprinting, yakni:
1. Modifikasi Asetilasi Histone
2. Modifikasi Metilasi DNA
1. Asetilasi HISTONE
(Aktif transkripsi)
Asetilasi residu lisine pd posisi terminus dr protein histone
menghilangkan 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
Acetylation (or ethanoylation): reaction that
introduces an acetyl functional 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.
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.
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.
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.
METILASI DNA
deaminasi
metilasi
Penambahan CH3 pada cytosine  Silencing Gene
Expression
Metilasi residu cytosine  5-methylcytosine
Deaminasi 5-methylcytosine  thymine.
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.
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").
DNA METHYLATION
After replication, daughter strands of fully methylated DNA are
hemimethylated (reaction 3) and the original pattern of DNA methylation
is maintained by the DNA methyltransferase (reaction 2), which
preferentially methylates the cytosine residues at hemimethylated CpG
sites.
Further replication without methylation of the hemimethylated DNA
results in fully unmethylated DNA (reaction 4).
De novo methylation (reaction 1) is also considered to be mediated by
the DNA methyltransferase, although the efficiency of de novo
methylation is low.
(Goto and Monk, 1998)
Regulation
The grouping of imprinted genes within clusters allows
them to share common regulatory elements, such as noncoding RNAs and differentially methylated regions (DMRs).
When these regulatory elements control the imprinting of
several genes in a given region, they are known as
imprinting control regions (ICR).
The expression of non-coding RNAs, such as Air on
mouse chromosome 17 and KCNQ1OT1 on human
chromosome 11p15.5, have been shown to be essential for
the imprinting of genes in their corresponding regions.
V. FENOTIPE, FENOKOPI, PLEIOTROPISM
GEN: Fragmen DNA yg mengkode suatu polipeptida
LOKUS : Lokasi gen pada kromosom
Kepentingan Lokus: Terapi gen & Rekayasa gen
Perbedaan antara linked & Unlinked Gene:
Linked gen: terletak pada kromosom yg sama;
Unllinked gen: terletak pada kromosom yang
berbeda.
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Hubungan antara GEN, ALLEL, & TRAITS (karakter)
GEN mempresentasikan traits
ALLELES = GENOTYPE  PHENOTYPE
T,t
Tinggi tanaman
T=tinggi / t=pendek
Interaksi ALEL akan menentukan karakter
Pada @ GEN, Individu diploid memiliki maks 2 Alel
Jk kedua alel sama  organisme disebut
HOMOZYGOUS
Jk kedua alel beda  HEROZYGOUS.
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FENOKOPI  keadaan fenotipe yg dipengaruhi
oleh faktor eksternal
PLEIOTROPISM  gen tunggal yg memiliki multi
efek
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VI. MALFORMASI KONGENITAL dan
FAKTOR-FAKTOR PENYEBAB
MALFORMASI KONGENITAL
• PENGERTIAN MALFORMASI KONGENITAL
• PERIODE KRITIS DARI PERKEMBANGAN
•TERATOLOGI
• FAKTOR PENYEBAB MALFORMASI
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PENGERTIAN MALFORMASI KONGENITAL
Katogori luas  "Congenital disorders"
 meliputi berbagai kondisi:
Minor physical anomalies (e.g., a birthmark),
Severe malformations of single systems (e.g.,
congenital heart disease or dysmelia),
Kombinations of abnormalities affecting several
parts of the body.
Congenital defects of metabolism
Ada 3 tipe utama congenital disorders:
1. Congenital physical anomalies
2. inborn errors of metabolism
3. Other genetic disorders
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PENGERTIAN MALFORMASI KONGENITAL
Congenital physical anomaly  abnormalitas
struktur dari suatu bagian tubuh.
Anomali  menjdi atau tidak menjadi masalah
Umumnya orang memiliki 1 atau lebih anomali
fisik
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Contoh anomali fisik:
- Anomali minor  kurvatura pd jari kelima
(clinodactyly)
- preauricular pits),
- Pemendekan tulang metacarpal / metatarsal ke-4
- dimples over the lower spine (sac dimples).
Bbrp anomali minor  indikasi adanya internal
anomali yg signifikan
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Malformasi kongenital
 jk anomali fisik bersifat hebat  cacat struktur 
masalah
malformation syndrome.
 Kombinasi malformasi  mempengarhi > 1 bagian
tubuh
Birth defect (Cacat lahir)
 istilah umum utk congenital malformation, i.e.
anomali fisik yg dikenali sehak lahir & secara
nyata merupakan masalah
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Genetic disorder / diseases
Semua mrpk kongenital, walaupun tidak tampak /
terekspresi
Genetic diseases, dibagi dalam :
Single-gene defects, multiple-gene disorders, atau
chromosomal defects.
Single-gene defects: akibat abnormalitas gen
autosomal (2 kopi/ recessive disorder) atau (1 kopi/
dominant disorder).
Bbrp akibat delesi atau abnormalitas beberapa gen
pada 1 kromosom
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Chromosomal disorders: hilangnya atau duplikasi
sebagian besar kromosom (ratusan gen) atau
kromosom intak (utuh)
Mempengaruhi bbrp bagian tubuh yg berbeda atau
sistem organ
Congenital metabolic disease: disebut inborn error
of metabolism.
Umumnya defek gen tunggal (diturunkan) 
mempengaruhi struktur atau fungsi bagian tubuh
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Congenital disorder  kondisi medis yg tampak
saat lahir.
Namun sebenarnya dapat dikenali sejak prenatal,
saat lahir atau saat dewasa atau tidak sama sekali
Congenital disorders Dapat diakibatkan oleh:
Abnormalitas genetik
Kondisi lingkungan intrauterine
Errors pd morphogenesis, atau
Unknown factors.
Congenital conditions Dapat merupakan suatu:
Penyakit, defek, disorders, anomalies, atau
perbedaan/variasi genetik
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Teratology (from the Greek τέρᾰς (genitive τέρᾰτος),
monster, atau marvel and λόγος,
Abad ke17  sesuatu yg tampak aneh/ abnormal
Abad ke19 berkaitan dgn biological deformities
medical study  teratogenesis,
congenital malformations atau individu dgn kelainan
bentuk makroskopis.
Dysmorphology  the study of abnormal form .
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PERIODE KRITIS PERKEMBANGAN
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FAKTOR-FAKTOR PENYEBAB MALFORMASI
KONGENITAL
1.
2.
3.
Endogenous
Exogenous
Multifactorial Inheritance
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Defek CNS Berdasarkan Waktu Terjadinya
A.
Neurulation Defects
1.
Primary
a.
anencephaly
b.
meningoencephalocele
c.
mylomeningocele
Secondary
a.
diastematomyelia
b.
tethered cord
Spina Bifida
a.
spina bifida occulta
b.
spina bifida cystica
2.
3.
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B.
Migration Defects
1.
2.
3.
4.
5.
Lissencephaly (agyria)
Pachygyria
Polymicrogyria
Cortical heterotropia
Schizencephaly
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PARASITIC
TWIN
TERIMA KASIH