Potter Lab

Hutchison CA 3rd, Newbold JE, Potter SS, Edgell MH. Maternal inheritance of mammalian mitochondrial DNA. Nature. 251: 536. 1974.

This Nature paper was the first demonstration of the maternal inheritance of mitochondrial DNA in mammals. It was also one of the early applications of restriction enzymes. We showed that the restriction digest patterns of mtDNA from donkeys and horses were quite distinct, and that the progeny of their reciprocal crosses, mules and hinnies, always had the same pattern as the mother.

The author order is a recurring issue of interest for my papers. I haven’t worried much about author order. For this paper I was the graduate student who did the experiments, purified the mtDNAs (a bit of a challenge at the time) and ran the digests and gels. The other three authors were professors who thought of the experiments and wrote the paper. I probably had a reasonable claim for first author, but told them I didn’t care, and ended up in the middle.

 
Supp D, Witte DP, Potter SS, Brueckner M. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature. 389:963-966. 1997.

This paper was the culmination of a huge effort by my graduate student and then postdoc Dorothy Supp. It describes the cloning of the gene responsible for the left right phenotype in the legless mutant, a dynein encoding gene that we named left right dynein, or LRD. After some discussion Supp and I decided to share the gene with Tina Brueckner at Yale, who had been trying to positionally clone the iv gene for several years. Brueckner then sequenced this gene and showed that the iv version had a single missense mutation at a critical position. Dave Witte showed that the gene is expressed at the node during early development. This work contributed to the development of the nodal flow model of left right development by a Japanese group.

 
Sheng HZ, Moriyama K, Yamashita T, Li H, Potter SS, Mahon KA, Westphal H. Multistep control of pituitary organogenesis. Science. 278, 1809-1812. 1997.

Sharma K, Sheng HZ, Lettieri K, Li H, Karavanov A, Potter SS, Westphal H,  Pfaff SL. LIM homeodomain factors Lhx3 and Lhx 4 assign subtype identities for motor neurons. Cell. 6:817-828. 1998.

These two were collaborations where we contributed the mutant mice.

 
Brunskill EW, Aronow BJ, Georgas K, Rumballe B, Valerius MT, Aronow J, Kaimal V, Jegga AG, Grimmond S, McMahon AP, Patterson LT, Little MH, Potter SS. Atlas of gene expression in the developing kidney at microanatomic resolution. Dev. Cell. 5;781-91. 2008.

This paper presents part of our kidney atlas project. We are now extending this effort to single cell types, and even single cells. We have also been funded to carry out a similar study of craniofacial development.

 
Potter SS, Brorein Jr. WJ, Dunsmuir P, Rubin GM. Transposition of elements of the 412, copia and 297 dispersed repeated gene families in Drosophila. Cell. 17: 415-427. 1979.

 
This paper was the first molecular demonstration of the presence of transposable elements, or jumping genes, in metazoans. The sequences of a couple of transposable element families had been previously cloned by members of the Hogness Lab. They did in situ hybridizations to the polytene chromosomes of Drosophila salivary glands and saw some differences in hybridization positions, but interpreted this to be the result of variations in polytenization of chromosomes in different strains, and not to reflect genuine differences in chromosome positions (See their Cold Spring Harbor paper of 1978).

In this paper we cloned “empty-filled” corresponding DNA sites from different Drosophila, showing that in some cases the site would have a transposable element and in other cases not. This clearly showed they could move about the genome. We also used reassociation kinetics to show that the copy number of the elements could dramatically increase in tissue culture cells, showing that in this situation the elements were de-repressed and moved and replicated like crazy. These results showed that the puzzling moderately repetitive fraction of DNA was in fact made up of jumping genes.

I was Gerald Rubin’s second postdoc. He went on to do rather well.

 
Potter S, Truett M, Phillips M, Maher A. Eukaryotic transposable genetic elements with inverted terminal repeats. Cell. 20: 639-647. 1981.

Truett M, Jones R, Potter S. Unusual structure of the FB family of transposable elements in Drosophila. Cell. 24:753-763. 1981.

 
These two papers were the first from my independent lab. The first represents work we did during my first year as an assistant professor. Mark Phillips and Drew Maher (senior author!) were undergraduates who worked in my lab part time. They were both outstanding. These papers described the discovery of a category of transposable element, the first that did not look like a retrovirus. We named them foldback, or FB, elements, because they carried inverted terminal repeats that could fold back on themselves following denaturation, forming pretty little stem loop lollipop structures when we looked at them with the electron microscope. Martha Truett and Richard Jones were my first graduate students. Truett went directly to industry to work for Chiron Corp. Jones went on to do a postdoc at Harvard and is now a professor at SMU, publishing high-profile (Science, Nature) papers on the subject of gene-expression memory.

 
Potter, SS. DNA sequence of a foldback transposable element in Drosophila. Nature. 297: 201-204. 1982.

This was a single author Nature article. You don’t see a lot of these. I did all the work on this one. It represented a fairly massive sequencing project at the time, revealing a very interesting direct repeat structure within the inverted repeats of the foldback elements.

 
Wichman H, Potter S, Pine D. Mys, a family of mammalian transposable elements isolated by phylogenetic screening. Nature. 317: 77-81. 1985.

This paper described some novel transposable elements in mouse and a general method for discovering new families of elements. Holly Wichman was my first postdoc. She got the lab started with the mouse model system. She went on to make quite a name for herself in the area of molecular evolution, serving on study sections, publishing good papers and becoming a professor. Dan Pine (senior author!) was an undergraduate working in the lab part time.

 
McNeish J, Scott W, Potter S. Legless, a novel mutation found in PHT1-1 transgenic mice. Science. 241:837-839. 1988.

This paper described a very interesting transgene insertional mutant we had made, with randomized left-right axis and severe limb defects. This mouse got us interested in laterality as well as limb and craniofacial development.

 
Mucenski ML, McLain K, Kier AB, Swerdlow SH, Schreiner CM, Miller TA, Pietryga DW, Scott Jr. WJ, Potter, SS. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell. 65:677-689. 1991.

This was one of the earliest gene-targeting papers. I think it was one of the first 10. It described a pretty interesting phenotype resulting from the c-myb oncogene targeted mutation. Mike Mucenski, a postdoctoral fellow, picked the gene and made the mouse. He now works at Cincinnati Children’s in the Division of Pulmonary Biology.

 
Davis AP, Witte DP, Hsieh-Li HM, Potter SS, Capecchi MR. Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature. 375:791-795. 1995.

The paper gave the most dramatic demonstration of the functional redundancy of paralogous Hox genes. We exchanged Hox mutant mice with the Capecchi Lab and we analyzed the soft tissues, such as kidney, while he analyzed skeletons. Single mutants had relatively normal limbs and kidneys, while double mutants had severely defective limbs, with the paw attached to the elbow, and kidneys that were extremely small or absent. Although the work was pretty evenly divided, my lab ended up as middle authors. I figured it was OK, because I thought Mario Capecchi would end up winning the Nobel Prize some day, which he did. He is a very interesting guy.

 
Lowe LA, Supp DM, Sampath K, Yokahama T, Wright CVE, Potter SS, Overbeek P, Kuehn MR. Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus. Nature. 381:158-161. 1996.

This was a collaboration in which Mike Kuehn’s lab did most of the work. We provided timed mutant embryos and he did in situ hybridizations. The results were pretty cool, showing randomized expression of left right markers in the legless mutants, with a quarter showing left side only Pitx2 expression (normal), a quarter showing right only, a quarter showing both sides and a quarter showing neither side.