The Developmental Control Of Tissue Growth And Organ Size

       The genetic control of organ size and cell proliferation is poorly understood. Our work addresses these questions from two different directions. In one, we ask how the Hox gene Ubx is able to reduce the number of cells in the haltere compared to the homologous wing. One important answer to this question is that Ubx appears to be modifying many different parameters of the Dpp pathway, including how far the Dpp morphogen can diffuse from its site of production. See Crickmore et al. 2006, 2007. In a second project we are asking how the Hippo tumor suppressor pathway, which is a core component of the cell proliferation machinery in nearly all tissues, is being used in a tissue-specific manner.  We found that while the Hippo pathway in wing cells use the transcription factor Scalloped (Sd), in eye progenitor cells they use the homeodomain protein Hth. Thus, we hypothesize that the choice of transcription factor can provide tissue-specificity to this otherwise generic proliferation-regulating pathway. See Peng et al., 2009 for more details.

 

Current lab members working on this project: Roumen Voutev, Susie Tozier

Recent papers:

Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning. Slattery M, Voutev R, Ma L, Nègre N, White KP, et al. PLoS genetics. 2013; 9(9):e1003753. PMID: 24039600 PMCID: PMC3764184

 

 

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Haltere (left) and wing (right) imaginal discs have the same overall morphology but differ in size. They also differ in that all haltere cells, but not wing cells, express the Hox protein Ubx, stained here in green.

 

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 Clones of cells (labeled in green) that mis-express Hth and the Zn-finger protein Teashirt (Tsh) overproliferate by inhibiting the Hippo pathway. See Bessa et al., 2002 and Peng et al., 2009.

 

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An eye imaginal disc stained for CycB and a marker of the morphogenetic furrow. CycB is expressed strongly ahead (anterior) of the furrow.

 

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A series of dorsal appendages that vary in size. The wild type wing is on top and the wild type haltere is on the bottom. See Crickmore 2006 for details.

 

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Differences in Dpp expression in the wild type haltere (left) compared to the wild type wing (right). See Crickmore, 2006 for details.

 

 

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Representative publications:

Bessa J, B. Gebelein, F. Pichaud, F. Casares, and R.S. Mann (2002) Combinatorial control of Drosophila eye development by Eyeless, Homothorax, and Teashirt. Genes Dev. 16:2415-2427.

 

 

Crickmore, MA and R.S. Mann (2006) Hox Control of Organ Size by Regulation of Morphogen Production and Mobility. Science (Article), 313(5783):63-8.

PDF: Crickmore+Mann_text+SOM

 

 

Crickmore MA, Mann RS. (2006) Hox control of morphogen mobility and organ development through regulation of glypican expression. Development. 2007 Jan;134(2):327-34.

PDF: Crickmore+MannDev

 

 

Peng, W., Slattery, M. and Mann RS. Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc. Genes Dev (2009) 23(19):2307-19.

PDF: Peng et al_G&D

 

 

 

The Laboratory of Richard S Mann
Department of Biochemistry and Molecular Biophysics
Columbia University Medical Center
701 West 168th Street, HHSC 1104
New York, NY 10032
212.305.2111

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