My proposed research seeks to uncover the precise developmental mechanisms by which gene regulatory complexity is translated through cellular behaviors into specific morphological outcomes. Achieving this constitutes a fundamental challenge in biomedical sciences, as errors in embryonic patterning often lead to congenital and postnatal abnormalities that can have The mammalian skin displays marked anatomical variation in growth, thickness, pigmentation, and types of cutaneous appendages. These regional differences arise during embryogenesis, suggesting that gene regulatory networks controlling skin development harbor a latent reservoir of anatomical complexity. To understand how such regulatory complexity is translated into spatial patterns of cellular differentiation, drastic consequences for individuals. my research program combines the study of diverse, naturally occurring phenotypes in emerging model species, with parallel studies in the laboratory mouse, where powerful molecular and genetic tools already exist. The proposed experiments seek to elucidate how the skin acquires, interprets, and executes positional information by focusing on two distinct spatially patterned phenomena during skin development (1) stripe pattern formation in rodents, using a system I established as a postdoc and (2) formation of gliding membranes in marsupials, using a system under development in my laboratory. The approaches described in the two research programs integrate multiple disciplines, including developmental biology, molecular biology, evolutionary genetics, and functional genomics, with my expertise in skin developmental biology (postdoctoral training) and demonstrated success developing molecular tools in emerging model species (graduate and postdoctoral training). By focusing on developmental mechanisms, this work will uncover the stepwise processes by which genetic information generates spatial patterns of cellular differentiation during embryogenesis, provide a comprehensive roadmap for linking genotype and phenotype at an unprecedented mechanistic and conceptual level, and will generate fundamental insights into the biology of mammalian skin, from the processes controlling skin development and homeostasis to the mechanistic bases of diseased states.

Public Health Relevance

The proposed research seeks to decipher the precise developmental mechanisms by which gene regulatory complexity is translated through cellular behaviors into specific morphological outcomes - an extremely pressing challenge in biomedical research, as errors in embryonic patterning often lead to congenital and postnatal abnormalities. My research integrates multidisciplinary approaches and combines the study of emerging model species, because of their diverse, naturally occurring phenotypes, with the laboratory mouse, because of the powerful molecular and genetic tools that already exist, to understand how the skin acquires, interprets, and executes positional information during embryogenesis. By focusing on developmental mechanisms, this work will uncover the stepwise processes by which genetic information generates spatial patterns of cellular differentiation during embryogenesis, provide a comprehensive roadmap for linking genotype and phenotype at an unprecedented mechanistic and conceptual level, and will generate fundamental insights into the biology of mammalian skin, from the processes controlling skin development and homeostasis to the mechanistic bases of diseased states.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
1R35GM133758-01
Application #
9798127
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Hoodbhoy, Tanya
Project Start
2019-09-13
Project End
2024-08-31
Budget Start
2019-09-13
Budget End
2020-08-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Graduate Schools
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08543