Asymmetric cell division.

Asymmetric cell division.

1. Asymmetric cell division. BY KAMAL TALIYAN B.Sc. ZOOLOGY HONS. ZOM 502

2. CONTENTS INTRODUCTION TYPES EXTRINSIC TYPE INTRINSIC TYPE ASYMMETRIC CELL DIVISION IN C. elegans. ASYMMETRIC CELL DIVISION IN Drosophila NEURAL DEVELOPMENT. ROLE IN DISEASE.

3. An asymmetric cell division -gives rise to two sister cells that have different fates, a feature that can be recognized by differences in- Size. Morphology. Gene expression pattern. The number of subsequent cell divisions. INTRODUCTION

4. ASYMMETRIC CELL DIVISION INTRINSIC ASYMMETRIC CELL DIVISION EXTRINSIC ASYMMETRIC CELL DIVISION According to Horvitz and Herskowitz there are two mechanisms by which asymmetric cell division can occur-

5. EXTRINSIC ASYMMETRIC CELL DIVISION T he daughter cells are initially equivalent but a difference is induced by signaling between the cells, from surrounding cells, or from the precursor cell. This mechanism is known as extrinsic asymmetric cell division.

6. INTRINSIC ASYMMETRIC CELL DIVISION T he prospective daughter cells are inherently different at the time of division of the mother cell. Because this latter mechanism does not depend on interactions of cells with each other or with their environment, it must rely on intrinsic asymmetry.

7. In multi-celled organisms this mechanism raises two requirements: The mother cell must be polarized; The mitotic spindle must be aligned with the axis of polarity. The cell biology of these events has been most traditionally studied in three animal models: the mouse, the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster . Recent work in spiralian development has also discovered insightful mechanisms of asymmetric cell division. contd...

8. In C. elegans , a series of asymmetric cell divisions in the early embryo are critical in setting up the anterior/posterior, dorsal/ventral, and left/right axes of the body plan. After fertilization, events are already occurring in the one cell stage embryo to allow for the first asymmetric cell division. This first division produces two distinctly different blastomeres, termed AB and P1. ASYMMETRIC CELL DIVISION IN C. elegans DEVELOPMENT .

9. Following this first asymmetric division, the AB daughter cell divides symmetrically, giving rise to ABa and ABp, while the P1 daughter cell undergoes another asymmetric cell division to produce P2 and EMS. This division is also dependent on the distribution of the PAR proteins. The establishment of this polarity initiates the polarized distribution of a group of proteins present in the zygote called the PAR proteins (partitioning-defective), which are a conserved group of proteins that function in establishing cell polarity during development.

10. In normal non-tumor stem cells, a number of genes have been described which are responsible for pluripotency, such as Bmi-1, Wnt and Notch. These genes have been discovered also in the case of cancer stem cells, and shows that their aberrant expression is essential for the formation of tumor cell mass.

11. In Drosophila melanogaster , asymmetric cell division plays an important role in neural development. Neuroblasts are the progenitor cells which divide asymmetrically to give rise to another neuroblast and a ganglion mother cell (GMC). The neuroblast repeatedly undergoes this asymmetric cell division while the GMC continues on to produce a pair of neurons. Two proteins play an important role in setting up this asymmetry in the neuroblast, Prospero and Numb. These proteins are both synthesized in the neuroblast and segregate into only the GMC during divisions. Asymmetric cell division in Drosophila neural development.

12. Other proteins present in the neuroblast mediate the asymmetric localization of Numb and Prospero. Miranda is an anchoring protein that binds to Prospero and keeps it in the basal cortex. Following the generation of the GMC, Miranda releases Prospero and then becomes degraded. The segregation of Numb is mediated by Pon (the partner of Numb protein). Pon binds to Numb and colocalizes with it during neuroblast cell division.

13. In normal stem and progenitor cells, asymmetric cell division balances proliferation and self-renewal with cell-cycle exit and differentiation. Disruption of asymmetric cell division leads to aberrant self-renewal and impairs differentiation, and could therefore constitute an early step in the tumorigenic transformation of stem and progenitor cells. Role of asymmetric cell division in disease

14. Another mutation in asymmetric cell divisions which are involved in tumor growth are loss-of-function mutations. The first suggestion that loss of asymmetric cell division might be involved in tumorigenesis came from studies of Drosophila. Studies of loss-of-function mutations in key regulators of asymmetric cell division including lgl, aurA, polo, numb and brat, revealed hyperproliferative phenotypes in situ. In these mutants cells divide more symmetrically and generate mis-specified progeny that fail to exit the cell cycle and differentiate, but rather proliferate continuously and form a tumor cell mass.

15. REFERENCES Image and gif courtesy: www.googleimages.com www.wikipedia.com www.nature.com www.ncbi.nlm.nih.gov www.sciencedirect.com

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