What the signal?!

Drosophila - canonical signalling

WNT signal protein

detected on cell membrane by Frizzeled (Fz) and LRP

activating Dishevelled (Dsh)

inhibiting ß-catenin destruction complex

—> Stabilization of ß-Catenin and Promotion of its entry into the nucleus where it acts as a TF recruiter of the LEF/TFC family

Drosophila - planar cell polarity PCP signalling

seperate signals from proximal and distal side play a role

Distal: Fz and Flamingo (Fmi) rezeptors activate Dsh which activates RHO and RHO kinase which are responsible for distal outgrowth of actin rich prehair

Proximal: Strabismus (Stbm) and Fmi rezeptors and Pickle (Pk) inhibit the distal outgrowth of actin rich prehair so everywhere their signal reaches (on proximal side) it wont grow hair

The rezeptor proteins stay on their side and maintain cell polarity for the cell even if there is no more signaling, they also inhibit the formation of the counter side rezeptors on their side

Canonical Wnt Pathway:

In the canonical Wnt pathway, the key mediator is β-catenin. When Wnt ligands bind to their receptors (Frizzled and LRP5/6), a signaling cascade is initiated, leading to the stabilization and accumulation of β-catenin in the cytoplasm. This stabilized β-catenin then translocates to the nucleus, where it interacts with TCF/LEF transcription factors and regulates the expression of target genes involved in various cellular processes.

Non-Canonical Wnt Pathways:

Non-canonical Wnt pathways are β-catenin-independent and involve intracellular signaling cascades that regulate cell polarity and movement. Two main non-canonical pathways are the Wnt/Ca2+ pathway and the planar cell polarity (PCP) pathway.

Cortical Rotation (of the Animal pole cortex towards the sperm entry point) creates the grey crecent at the dorsal side (opposite to sperm entry point [ventral]) on the dorsal side ß-Catenin is activated

on the vegetal pole of the egg TGF-ß signal is active on the point where ß-catenin and TGF-ß overlap the Nieuwkoop center will form

TGF-ß (tranforming growth factor) is a zytokin superfamiliy NODAL or BMP are members of that superfamily

Notch is the receptor to ligand Delta (or Jagged proteins) —> all transmembrane proteins

1. Proteolytic Cleavage: Notch receptors exist in a single-pass transmembrane form. Upon binding of a ligand (e.g., Delta) to the Notch receptor on the adjacent cell, the Notch receptor undergoes a series of proteolytic cleavages. The first cleavage is catalyzed by ADAM (a disintegrin and metalloprotease) proteases, leading to the release of the extracellular portion of Notch.

2. γ-Secretase Cleavage: The remaining transmembrane portion of Notch is then subjected to a second cleavage, catalyzed by γ-secretase. This cleavage releases the Notch intracellular domain (NICD) from the membrane and allows it to enter the nucleus.

3. Nuclear Translocation: The NICD translocates into the nucleus, where it forms a complex with a transcription factor known as CSL (CBF1/Suppressor of Hairless/Lag-1). This complex is also referred to as the "Notch transcriptional activation complex."

4. Target Gene Activation: The NICD-CSL complex acts as a transcriptional activator, promoting the expression of target genes such as Hes (Hairy and Enhancer of Split) and Hey (Hes-related with YRPW motif). These target genes are involved in various cellular processes, including cell fate determination, differentiation, and proliferation.

5. Cell Fate Decisions: Notch/Delta signaling is known for its role in mediating cell fate decisions. Depending on the cellular context and the specific target genes activated, Notch signaling can promote the adoption of one cell fate over another. This process is particularly important during embryonic development and tissue homeostasis.

6. Feedback Regulation: Notch signaling is tightly regulated by feedback mechanisms, including the expression of inhibitors like Numb, which can interfere with the activation of Notch receptors.

it decides cell fates and causes lateral inhibition so cells around wont join same cell fate

e.g. vulva developement in C. elegans (Notch/lin12 and Delta/Lag2 ligand)

1. Synthesis and Release: Sonic hedgehog is initially synthesized as a precursor protein. This precursor undergoes processing and modification to become the active Sonic hedgehog protein, which is then released from the producing cells.

2. Reception by Receptor: The Sonic hedgehog protein binds to a cell surface receptor called Patched (Ptch). Ptch inhibits another protein called Smoothened (Smo) in the absence of Sonic hedgehog binding.

3. Inhibition of Suppressor Proteins: When Sonic hedgehog binds to Ptch, it relieves the inhibition of Smoothened (Smo). Activated Smo then inhibits a complex of proteins (Gli proteins) that act as transcriptional suppressors. This leads to the activation of the Hedgehog signaling pathway.

4. Activation of Gli Proteins: Gli proteins are transcription factors that, when released from inhibition, translocate into the nucleus of the cell. In the nucleus, they activate the transcription of target genes that are crucial for various developmental processes.

Bone Morphogenetic Protein

1. BMP Ligands: The pathway is initiated by the binding of BMP ligands to cell surface receptors. BMPs are a group of proteins that belong to the transforming growth factor-beta (TGF-β) superfamily. BMP ligands are produced and secreted by cells, and they play a crucial role in regulating cell differentiation and tissue development.

2. Receptor Activation: BMP receptors, which are serine/threonine kinase receptors, exist as complexes of type I and type II receptors. Upon BMP ligand binding, the type II receptors phosphorylate and activate the type I receptors.

3. Smad Activation: Activated type I receptors phosphorylate a group of intracellular signaling proteins called Smads. Smads are key mediators of BMP signaling. Once phosphorylated, Smads form complexes with other regulatory proteins and translocate into the nucleus.

4. Nuclear Transcription: Inside the nucleus, the Smad complexes, along with other co-factors, regulate the transcription of target genes. This transcriptional regulation influences cell fate, differentiation, and other cellular responses.

5. Gene Expression and Cellular Response: The activation of BMP signaling leads to the expression of specific target genes that are critical for various cellular processes. These processes include the regulation of cell proliferation, apoptosis, and differentiation, depending on the cell type and context.

6. Feedback Regulation: BMP signaling is tightly regulated by various feedback mechanisms to maintain homeostasis. Inhibitory Smads (I-Smads) and other regulatory proteins help modulate the intensity and duration of the BMP signal.

7. Cellular Context and Crosstalk: The cellular response to BMP signaling is highly context-dependent. The same BMP ligand can have different effects on different cell types or at different stages of development. Additionally, BMP signaling often crosstalks with other signaling pathways, such as Wnt and Notch, to integrate multiple signals and coordinate complex developmental processes.