Cell migration occurs very early in the rabbit's embryonic development. Yellow represents the neural tube/spinal cord and blue is initial location of embryonic neural crest. The picture is only an visual example.
Parts of the Gastrointestinal (GI) tract that are affected by MC.
Genetically Inherited Megacolon
During the very early (in utero) development stages there is a reduced innervation (supply) of nerves, from the neural crest, to parts of the GI tract and the skin/fur. As a result a rabbits that inherits two of the dominant English spotting genes will have limited color spotting (on the fur/skin) along with a reduced number of "pacemaker nerve cells" in parts of the GI tract.
The number of neurons (myenteric), in the outer muscle wall in parts of the GI tract (myenteric plexus), is "significantly reduced" when compared to a rabbit that does not inherit two of the dominant English spotting genes (En/En). These neurons control the rate and strength that the outer muscle wall contracts that helps move things along. With a reduced number of neurons the muscle can contract abnormally. This can cause the material, moving through a rabbit's cecum and ascending colon, to move at an inconsistent pace producing abnormal size and shaped fecal and cecal pellets. This can lead to a slowdown or blockage increasing the size of the colon. This is where the term Megacolon comes from.
A study done in 2014, by a group at the University of Bologna in Italy, took a look at megacolon in the domestic rabbit Oryctolagus cuniculus (European rabbit) using the Checkered Giant breed. The results pointed to the "KIT" (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) gene as being responsible. Link to studies.
The KIT gene provides instructions for making a protein that transmits signals from the cell surface into a cell (protein signaling).
The KIT gene controls many vital cellular processes such as cell division and movement (migration). It also is important for the development of cells in the gastrointestinal tract (interstitial cells of Cajal [ICCs]) and cells called melanocytes (melanocytes produce the pigment melanin, this contributes to skin and fur coloring).
Results of the KIT gene in action. Two rabbits from the same litter. The male rabbit on the left had light spotting and had MC. The female on the right did not have MC.
"Mechanical" or "Acquired" Megacolon
Sometimes a rabbit can get the same symptoms as a genetic En/En rabbit but through "mechanical" means such as spinal cord fracture, injury, or disease, amoung with other traumatic events. An example would be the loss of mobility in the hind legs that could causes MC like symptoms.
Some rabbits can also "acquire" the same type of problems which can be the result of a surgery interfering with the nerves that regulate the GI tract. This sometimes can't be helped and shows up as a post-op complication. EC damage can also mimic megacolon.
Area affected by MC.
Outer muscle wall of colon affected by MC.
Derived from a picture by Goran tek-en [CC BY-SA 3.0], via Wikimedia Commons
Cross section: affected location of reduced nurons.
Reprinted & adapted by permission from Macmillan Publishers Ltd: Mucosal Immunology, 328-329. doi:10.1038/mi.2008.25, copyright 2008.