The core canonical machinery that orients the spindle consists of Gα proteins, Pins/LGN, Mud/NuMA and cytoplasmic Dynein
Additional factors (INSCUTEABLE (INSC), DLG etc.) can be context dependent
Context dependent positioning factors provide spatial information for spindle orientation (PAR complex etc...)
Subcomplexes form in this system to coordinate the positioning of the mitotic spindle
Mud/NuMA: mitotic antigens, that is a cargo of Dynein, and has the ability to engage with further molecules
To position this machinery: Cofactors
influencing cell choice fate: by shifting the orientation of the mitotic spindle system, it chooses what parts of the cell are inherited by the daughter cell.
influencing cell choice fate: by
shifting
the orientation of the mitotic spindle system, it chooses what parts of the cell are inherited by the daughter cell.
Example: Symmetric and asymmetric stem cell division in the mammalian muscle for rapid repairs…
The machinery that orients the spindle in Drosophila neuroblasts
The PAR polarity complex and INSCUTEABLE protein serve as positioning factors
PAR polarity complex assembles allowing an asymmetric recruitment of INSCUTEABLE protein (aligns the mitotic spindle)
They bind to the membrane & they have a patterning system that restricts them to one side of the cell.
How to keep the right balance? different stem cell division modes
1) Neuroblasts can polarize in a cell autonomous manner
2) When allowed to repolarize, the orientation of the polarity axis changes
Neuroblasts interpret a signal from the last-born daughter cell to orient the subsequent division
3) Cortex glia protect neuroblast against environmental stresses (e.g. oxidative stress)
How is the cell fate information provided ? How do cells determine in which way to orient the spindle?
Extrinsic signals: by the position during the cell division (e.g. signaling from neighboring cells/ Microenvironment)
Intrinsic signals: asymmetric localization of fate information in form of Proteins, mRNA, organelles etc. >>> e.g. how in fruit fly the loss of cell polarity affects the cell cycle mechanisms in neuroblasts resulting in tumours
Drosophila male germ line stem cell divisions are oriented by contact with neighboring hub cells
Budding yeast can orient its division using a the “bud scar” from the previous division
How can a cell control the right balance between having progenitor cells and dividing ?
Stem cell division mode (asymmetric/symmetric) can be controlled by the orientation of stem cell division
* Spindle orientation can control Tissue architecture and morphogenesis (= the generation of form)
Last changed2 years ago
