Richard S. Mann, PhD
- Higgins Professor of Biochemistry and Molecular Biophysics
Control of pattern formation by homeotic genes and their downstream targets in Drosophila.
Our lab uses the fruit fly, Drosophila melanogaster, to study three main problems: Hox protein function and specificity; appendage development; and the development and function of the adult motor system. Our work on Hox proteins centers around two questions: 1) how these homeodomain-containing transcription factors achieve specificity in vivo and 2) what are the relevant target genes that these factors regulate to control morphogenesis? To answer these questions, we are using a variety of in vitro DNA binding assays, structural biology, in vivo reporter gene assays, and genome-wide methods to discover and validate Hox target genes and Hox binding sites. Genetic methods are used to analyze the function of putative target genes and their specific contributions to morphology. Our work on appendage development focuses on two questions: 1) how is positional information generated along the proximo-distal (PD) axis and 2) how is cell proliferation regulated and coordinated with cell differentiation? To answer the first question, our main approach is to dissect at high resolution the transcriptional responses of genes expressed at specific positions along the PD axis, primarily in the legs. To answer the second question, we are identifying the genes and pathways that selector genes regulate to modulate cell proliferation during appendage development. Our work on the adult motor system stems from our work on leg development. Here, we are studying how the motor neurons that innervate the adult leg are generated and specified to target the correct muscles and generate the correct dendritic pattern in the CNS. Using this information, we are beginning to study how the movement of the legs is coordinated by local interneurons and sensory feedback. Locomotion assays to study adult walking behavior are used to analyze the wild type circuitry and the consequences to when this circuit is perturbed.
Up to date information on the Mann lab can be found at https://mannlab.zuckermaninstitute.columbia.edu/
- Axon Pathfinding and Synaptogenesis
- Cell Specification and Differentiation
- Cellular/Molecular/Developmental Neuroscience
- Stem Cell Biology
- Mendes CS, Bartos I, MÃ¡rka Z, Akay T, MÃ¡rka S, Mann RS. Quantification of gait parameters in freely walking rodents. BMC Biol. (2015) Jul 22;13:50. doi:10.1186/s12915-015-0154-0. PMID: 26197889.
- Enriquez J, Venkatasubramanian L, Baek M, Peterson M, Aghayeva U, Mann RS. Specification of individual adult motor neuron morphologies by combinatorial transcription factor codes. Neuron. (2015) May 20;86(4):955-70. doi:10.1016/j.neuron.2015.04.011. Epub 2015 May 7. PMID: 25959734; PMCID: PMC4441546.
- Abe N, Dror I, Yang L, Slattery M, Zhou T, Bussemaker HJ, Rohs R, Mann RS. Deconvolving the recognition of DNA shape from sequence. Cell. (2015) Apr 9;161(2):307-18. doi: 10.1016/j.cell.2015.02.008. Epub 2015 Apr 2. PMID: 25843630; PMCID: PMC4422406.
- Bouchard MB, Voleti V, Mendes CS, Lacefield C, Grueber WB, Mann RS, Bruno RM, Hillman EM. Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms. Nat Photonics. (2015) Feb;9(2):113-119. PMID: 25663846; PMCID: PMC4317333.
- Crocker J, Abe N, Rinaldi L, McGregor AP, Frankel N, Wang S, Alsawadi A, Valenti P, Plaza S, Payre F, Mann RS, Stern DL. Low affinity binding site clusters confer hox specificity and regulatory robustness. Cell. (2015) Jan 15;160(1-2):191-203. doi: 10.1016/j.cell.2014.11.041. Epub 2014 Dec 31. PMID: 25557079; PMCID: PMC4449256.
- Mendes CS, Rajendren SV, Bartos I, MÃ¡rka S, Mann RS. Kinematic responses to changes in walking orientation and gravitational load in Drosophila melanogaster. PLoS One. (2014) Oct 28;9(10):e109204. doi: 10.1371/journal.pone.0109204. eCollection 2014. PMID: 25350743; PMCID: PMC4211655.
- Agelopoulos M, McKay DJ, Mann RS. cgChIP: a cell type- and gene-specific method for chromatin analysis. Methods Mol Biol. (2014);1196:291-306. doi:10.1007/978-1-4939-1242-1_18. PubMed PMID: 25151171; PMCID: PMC4439094.
- Slattery M, Voutev R, Ma L, NÃ¨gre N, White KP, Mann RS. Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning. PLoS Genet. (2013) 9(9):e1003753. doi:10.1371/journal.pgen.1003753. Epub 2013 Sep 5. PMID: 24039600; PMCID: PMC3764184.
- Mann RS. Neuroscience. The Michael Jackson fly. Science. (2014) Apr 4;344(6179):48-9. doi: 10.1126/science.1252431. PMID: 24700848; PMCID: PMC4143233.
- Baek M, Enriquez J, Mann RS. Dual role for Hox genes and Hox co-factors in conferring leg motoneuron survival and identity in Drosophila. Development. (2013) May;140(9):2027-38. doi: 10.1242/dev.090902. Epub 2013 Mar 27. PMID: 23536569; PMCID: PMC3631975.