How the body becomes asymmetric
Jan 19,2007 00:00 by

Re­search­ers say they’ve learn­ed a sur­pris­ing fact about cell di­vi­sion that might help ex­plain how we be­come asym­met­ric—with the heart on the left, and two dif­fer­ent brain halves, for in­stance.

It seems that when cells di­vide, they some­times dis­t­rib­ute their DNA dif­fer­ently among “daugh­ter” cells, said Amar J. S. Klar of the Na­tion­al Can­cer In­s­ti­tute at Fred­er­ick, Md. 

The left-right dy­nein is one of 12 pro­teins form­ing the dy­nein mo­tor, a ti­ny ma­chine that per­forms trans­por­ta­tion tasks in a cell. The mo­tor is shown sche­mat­i­cal­ly above. Its two green, egg-shaped ends grab on­to a "microtubule," a type of struc­tur­al ca­ble with­in a cell. The op­po­site end of the mol­e­cule com­plex at­taches it­self to some "car­go." The green ends then "walk" along the cord to move the car­go. (Cour­te­sy ORNL.) 
He and a col­league pre­sented a stu­dy on the sub­ject in in the Jan. 5 is­sue of the re­search jour­nal Sci­ence.

When cells re­p­ro­duce, they first rep­li­cate each of their chro­m­o­somes, which con­t­ain the genes. One copy of each chro­mo­some, called a chro­ma­tid, then goes to each daugh­ter cell. 

Sci­en­tists tra­di­tion­ally thought that for a giv­en chro­mo­some, which cell gets which chro­ma­tid is ran­dom. But Klar and Atha­na­sios Ar­mako­las, now at the Hip­po­kra­te­ion Hos­pi­tal of Ath­ens, found that in mice, this dis­tri­bu­tion is ran­dom in some cell types but not oth­ers.

When it’s not, the “bi­as” in dis­tri­bu­tion de­pends on the pres­ence of a pro­tein mol­e­cule called left-right dynein, the re­search­ers said. This is part of a small mo­lec­u­lar “mo­tor” be­lieved to drag chro­mo­somes to their des­ti­na­tions in daugh­ter cells.

The new find­ings thus sug­gest the pro­tein may also help de­cide which chro­ma­tid goes to which daugh­ter cell, Klar ar­gued.

How it might do this is un­known, but it’s “sus­pi­cious that a dynein mo­tor pro­tein—a fam­i­ly [of pro­teins] whose mem­bers are in­volved in chro­mo­some move­men­t—af­fect chro­ma­tid seg­re­ga­tion,” wrote Car­men Sapienza of Tem­ple Uni­ver­si­ty Med­i­cal School in Phil­a­del­phia, in a com­men­tary pub­lished with Klar’s pa­per in the jour­nal.

Pre­vi­ous stud­ies al­so found that left-right dynein af­fects the asym­me­try in bo­d­ily or­gans, said Klar. In 1959, Amer­i­can re­search­ers found that mice with mu­ta­tions in the gene for left-right dy­nein had a ran­domized struc­ture: half de­vel­oped in­sides that were mir­ror im­ages of the nor­mal.

It thus seems “very like­ly” that the asym­met­ric cell rep­li­ca­tion, due to this mo­lec­u­lar mo­tor, helps de­ter­mine the or­gan asym­me­try, Klar said. “The plot comes around in a cir­cle; it is too good to be a mere co­in­ci­dence,” he wrote in an e­mail.

In­di­vid­u­ally, though, each dynein-mutated mouse was still asym­met­ric, the 1959 study found. That is, or­gans in one in­di­vid­u­al would be slight­ly dif­fer­ent on the left and right. Thus, the dynein gene seems to de­ter­mine the dis­tri­bu­tion of asym­me­try—not the fact of asym­me­try it­self, Klar said. Sev­er­al oth­er genes are known to af­fect the lat­ter, he added, though these don’t re­late to mo­lec­u­lar mo­tors.