Developmental biology paracrine factors and signalling pathways
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PARACRINE FACTORS PRESENTED BY NAVDEEP KAUR M.Sc.ZOOLOGY (1 st semester) DOLPHIN PG COLLEGE OF SCIENCE AND AGRICULTURE DATE- 21.10.2019
AUTOCRINE SIGNALING Cell synthesizes a molecule for which it has its own receptor. E.g . Immune cells
ENDOCRINE SIGNALING Endocrine factors travel through the blood to exert their effect. E. g .Insulin
JUXTACRINE SIGNALING Cell membrane proteins on one cell surface interact with receptor proteins on adjacent cell surfaces. E.g . Notch signalling
PARACRINE SIGNALING Is a form of cell signalling in which the target cell is near the signal- releasing cell. Inducers (diffusible factors) synthesized by one cell diffuse over short distances to interact with other cell.
PARACRINE FACTORS The diffusible proteins(Inducer) responsible for paracrine signalling are called as paracrine factors or growth and differentiation factors(GDFs), acting as ligands.
PARACRINE FACTORS Paracrine factors are secreted into the immediate spaces around the cell. Paracrine factors function by binding to a receptor that initiates a series of enzymatic reactions within the cell. Paracrine factors act by signal transduction pathways either by activating a pathway directly or by blocking the activity of an inhibitor of a pathway ( inhibiting an inhibitor, as is the case with hedgehog signalling).
PARACRINE FACTORS FAMILIES The four groups of GDFs include: Fibroblast growth factor (FGF) family The hedgehog family The Wnt (Wingless) family Transforming growth factor- β (TGF- β ) families
FIBROBLAST GROWTH FACTOR Approximately two dozen FGF genes that have been identified, and they can produce hundreds of protein isoforms by altering their RNA splicing or their initiation codons . FGF activate fibroblast growth factor receptor (FGFRs) in turn, these receptors activate various signalling pathways. FGFR FGF RTK PATHWAY
FGF1 protein is important during regeneration. FGF2 in angiogenesis. FGF7 or keratinocyte growth factor is critical for skin development. FGF8 for limb development and lens induction. FGF MEMBERS
The receptor for the hedgehog family is Patched , which binds to a protein called Smoothened. Works by inhibiting an inhibitor. Hedgehog pathway HEDGEHOG FAMILY Constitute members which are used by : embryo to induce particular cell types and to create boundries between tissues.
There are three hedgehog genes: Desert hedgehog ( dhh ) expressed in sertoli cells of testes. Indian hedgehog ( ihh ) expressed in gut and in cartilage and also important for postnatal bone growth. Sonic hedgehog involved in : Limb patterning Neural tube induction Somite differentiation
WNT FAMILY Wnts are a family of cysteine- rich glycoproteins. There are atleast 15 members of wnt family in vertebrates. WNT PATHWAY Wnt family intreract with transmembrane receptors of the frizzled protein which activates dishevelled protein. Works by inhibiting an inhibitor.
WNT PROTEINS Wnt proteins are involved in regulating: -specification of midbrain. - somites . -polarity of insect and vertebrate limbs. -proliferation of stem cells. -several steps in urinogenital system development.
TGF-β SUPERFAMILY The TGF- β superfamily has more than 30 members and includes: Transforming growth factor β (TGF- β ) family The activin family Bone morphogenetic proteins (BMPs) Vg1 family Glial- derived neurotrophic factor (GNDF) Mullerian inhibitory factor (MIF) SMAD PATHWAY
TGF- β SUPERFAMILY MEMBERS TGF-β members are important for: Extracellular matrix formation Epithelial branching that occurs in lung, kidney and salivary gland development BMPs regulate: Cell division Apoptosis Cell migration and differentiation BMP4 bone development Activin specify: Mesoderm (different region) Vertebrate axis (left and right sides)