Jyoti Misra
Stony Brook University, NY·Genetics
Organs have to end up the right size and the right shape, which means growth and tissue folding must be coordinated as an animal develops. Two cell-surface adhesion proteins, Dachsous and Fat, sit at the center of that coordination: they are evolutionarily conserved cadherins that pair up between neighboring cells, with Fat feeding into the Hippo pathway that limits how much a tissue grows, and Dachsous helping orient cells consistently across a tissue (planar cell polarity).
- Fields
Genetics
Biology
Biochemistry
- Topics
Fat cadherin
Dachsous
protocadherin
- Grants
- 1 known grant, through Aug 2027
What they work on
- Test how the endocytic machinery that internalizes surface proteins, together with a competitive inhibitor, establishes and maintains the spatial organization of Dachsous–Fat signaling across Drosophila tissues.
- Determine how Dachsous–Fat cell-cell junctions are remodeled by endocytosis in a mechanosensitive manner to permit the cell rearrangements of morphogenesis.
- Characterize a regulatory motif in the Fat cytoplasmic tail and its binding partners that recycle Fat back to the plasma membrane, and define how this motif controls where Fat sits on the cell surface.
- Determine how Fat restrains tissue growth through the Hippo pathway via Dachs, an atypical myosin motor protein, using Drosophila genetics.
- Examine how Fat signaling alters morphogen gradients and organ shape, using live imaging with quantitative image analysis to pinpoint the cellular rearrangements responsible in Fat mutant tissues.
More about the research
When these genes are mutated in people, the result is Van Maldergem and Hennekam syndromes, congenital disorders affecting multiple organ systems, and the same genes are implicated in several cancers. Yet basic questions remain open: how the pathway's spatial arrangement across a tissue gets set up and kept, how Dachsous–Fat contacts are taken apart and rebuilt so cells can rearrange during shape change, how Fat actually controls Hippo signaling, and how Fat determines organ shape.
Why it matters
Mutations in the Dachsous and Fat genes cause Van Maldergem and Hennekam syndromes, congenital disorders with defects across multiple organ systems, and the same pathway is altered in several cancers. Working out mechanistically how these proteins coordinate tissue growth with tissue shaping could explain how such birth defects arise and clarify how loss of growth control contributes to tumors.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kenneth Irvine
Rutgers University-New Brunswick, NJ·Biology
Determine how phase-separated condensates of Warts with Jub, and Jub-promoted phosphorylation of the Warts N-terminus, inhibit this Hippo pathway kinase in Drosophila tissues.
Maureen Cetera
University of Minnesota, MN·Biology
Identify directional cues that coordinate Planar Cell Polarity across the mouse epidermis, using natural mouse variants with region-specific hair misorientation and a candidate-gene approach.
Anna Sokac
University of Illinois Urbana-Champaign, IL·Biology
Test whether measurable features of transcription of five actin-regulator genes explain the even, synchronized timing of cellularization in Drosophila embryos, using live imaging of mRNAs down to single molecules.
The school
Stony Brook University: 32 labs on PI Pages, $319M a year on research, 289 research doctorates a year.
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