Hertwig's rule, or the long axis rule states that a

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

divides along its

long axis Long axis may refer to: * Long axis of organs in anatomy * Longitudinal axis of flight control surfaces {{dab ...

. Introduced by the German zoologist

Oscar Hertwig Oscar Hertwig (21 April 1849 in Friedberg – 25 October 1922 in Berlin) was a German embryologist and zoologist known for his research in developmental biology and evolution. Hertwig is credited as the first man to observe sexual reproduction ...

in 1884, the rule emphasizes the cell shape as a default mechanism of

spindle apparatus In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...

orientation. Hertwig's rule predicts cell division orientation, which is important for tissue architecture, cell fate and

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of devel ...

Discovery

Hertwig's experiments studied the orientation of frog egg divisions. The frog egg has a round shape and the first division occurs in a random orientation. Hertwig compressed the egg between two parallel plates. The compression forced the egg to change its shape from round to elongated. Hertwig noticed that elongated egg divides not randomly, but orthogonally to its long axis. The new daughter cells were formed along the longest axis of the cell. This observation thus became known as 'Hertwig's rule' or 'long axis rule'.

Confirmation and mechanism

TCJ orients spindle apparatus during cell division

Recent studies in animal and plant systems support the 'long axis rule'. The studied systems include the mouse embryo, ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

, ''

Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known ...

blastomeres In biology, a blastomere is a type of Cell (biology), cell produced by cleavage (embryo), cell division (cleavage) of the zygote after fertilization; blastomeres are an essential part of blastula formation, and blastocyst formation in mammals. Hum ...

(Strauss 2006), MDCK cell monolayers and plants (Gibson et al., 2011). The mechanism of the 'long axis rule' relies on

interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...

cell long axis sensing. However, during division many animal cell types undergo cell rounding, causing the long axis to disappear as the cell becomes round. It is at this rounding stage that the decision on the orientation of the cell division is made by the

. The spindle apparatus rotates in the round cell and after several minutes the spindle position is stabilised preferentially along the interphase cell long axis. The cell then divides along the spindle apparatus orientation. The first insights into how cells could remember their long axis came from studies on the ''Drosophila'' epithelium. The study indicated the participation of

tricellular junctions {{Short pages monitor