Skin patterning
Our lab investigates the developmental and evolutionary mechanisms that generate diversity and novelty in mammalian skin. This system provides a powerful model because it displays remarkable structural and functional variation across species, is experimentally accessible, and rests on a well-characterized molecular foundation. We pursue these questions through interconnected research areas. First, using the African striped mouse (Rhabdomys pumilio) as a model, we study the developmental basis and evolutionary origins of animal coat patterns. Second, by pioneering the marsupial sugar glider (Petaurus breviceps) as a novel model, we investigate the development and evolution of mammalian gliding membranes.
Mechanisms underlying stripe pattern formation and evolution
Many rodent species have evolved periodic pigmentation patterns (i.e., stripes and spots), which result from underlying differences in hair color. Periodic patterns in rodents are extremely stereotyped, suggesting a very tight genetic regulation of the temporal and spatial cues underlying their formation. How do skin cells receive, interpret, and execute the relevant information to generate such patterns? How are these mechanisms modified to produce pattern diversity? We are using pigment pattern formation in African striped mice (Rhabdomys pumilio) and other striped rodents as models to understand how the skin acquires positional information and how this information is modified to generate variation.
In recent studies, we uncovered a mechanism responsible for establishing and implementing color patterns and we found that development determines the type of color patterns that can evolve. Additionally, we have developed a variety of functional tools to study the mechanistic basis of pigment pattern formation.
Building on this work, our current projects address two fundamental questions in pattern formation: (1) How do tissues acquire positional information? We are investigating the developmental and regulatory mechanisms that generate dorsoventral Wnt modulator patterns in the striped mouse, focusing on the regulatory architecture of Sfrp2. (2) How is positional information modified? Through comparative studies of striped mice and the independently evolved Thirteen-Lined Ground Squirrel (Ictidomys tridecemlineatus), we are uncovering how skin developmental programs diversify to produce distinct stripe patterns.
Many rodent species have evolved periodic pigmentation patterns (i.e., stripes and spots), which result from underlying differences in hair color. Periodic patterns in rodents are extremely stereotyped, suggesting a very tight genetic regulation of the temporal and spatial cues underlying their formation. How do skin cells receive, interpret, and execute the relevant information to generate such patterns? How are these mechanisms modified to produce pattern diversity? We are using pigment pattern formation in African striped mice (Rhabdomys pumilio) and other striped rodents as models to understand how the skin acquires positional information and how this information is modified to generate variation.
In recent studies, we uncovered a mechanism responsible for establishing and implementing color patterns and we found that development determines the type of color patterns that can evolve. Additionally, we have developed a variety of functional tools to study the mechanistic basis of pigment pattern formation.
Building on this work, our current projects address two fundamental questions in pattern formation: (1) How do tissues acquire positional information? We are investigating the developmental and regulatory mechanisms that generate dorsoventral Wnt modulator patterns in the striped mouse, focusing on the regulatory architecture of Sfrp2. (2) How is positional information modified? Through comparative studies of striped mice and the independently evolved Thirteen-Lined Ground Squirrel (Ictidomys tridecemlineatus), we are uncovering how skin developmental programs diversify to produce distinct stripe patterns.
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Mechanisms of gliding membrane formation and evolution
Gliding membranes are specialized structures that develop along the dorso/ventral boundary of the skin and have evolved independently in at least six different mammalian lineages. We are trying to uncover the spatial and temporal signals that instruct this tissue to form and expand. What is the molecular nature of these signals? Are the same signals used by taxa as divergent as rodents and marsupials? We are studying the genomic and developmental mechanisms of gliding membrane formation in sugar gliders and flying squirrels to understand how novel structures originate. In recent work, we uncovered a gene regulatory network underlying gliding membrane formation and we found a mechanism that repeatedly evolved to pattern the same trait in different species. |
Building on this work, we are addressing three central questions in mammalian tissue patterning: (1) How is the patagium signaling center established? Using spatial transcriptomics and Wnt5a gain- and loss-of-function assays, we are identifying cell-type-specific regulatory networks essential for patagium development. (2) How do transcriptional programs integrate with mechanical forces to shape morphogenesis? Through quantitative assays, live imaging, atomic force microscopy, and viral perturbations, we are studying how Wnt5a, matrix proteins, and tissue properties interact. (3) What upstream mechanisms control spatial expression of key patagium genes? We using chromatin conformation and enhancer reporter assays to uncover the cis-regulatory logic of Emx2.
Beyond skin: Harnessing the rich biology of non-traditional species to uncover the mechanistic basis of phenotypic traits
In addition to skin traits, our lab studies the molecular basis of traits that confer ecological advantages to species. Many of our ongoing projects draw on the rich biology of striped mice and sugar gliders and leverage the molecular and genomic resources we have developed.
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- We recently uncovered genomic changes underlying the evolution of diurnality. Using the striped mouse—which shifted from the nocturnal niche of its relatives to a diurnal one—we combined whole-genome sequencing, transcriptomics, comparative genomics, and retinal functional assays to uncover how species adapt to new environments. Our results revealed major changes in circadian organization and showed that the visual system has been a key target of selection during this transition (collaboration with R. Lucas - U Manchester). - We discovered how marsupial neonates combat pathogens despite their immature immune systems. We showed that sugar glider cathelicidin antimicrobial peptides are highly expressed in neonates, regulated by enhancer sharing and long-range gene cluster interactions. These peptides modulate immune responses, display potent antimicrobial activity, and include one that protects mice from sepsis. We also found that marsupials and monotremes uniquely retain two cathelicidin clusters, linking their evolution to life history–specific immune needs (collaboration with M. Donia - Princeton). - We uncovered the neurobiological basis of paternal care in striped mice. In African striped mice, fathers and even unrelated alloparents naturally provide care, offering a unique model for paternal behavior. Using brain-wide activity mapping, single-nucleus RNA-seq, targeted gene manipulation, and environmental manipulations, we identified the medial preoptic area (MPOA) as a key hub for paternal care. Within the MPOA, we discovered a novel role for Agouti as a molecular integrator of socio-environmental cues: its overexpression drives infanticide, while suppression fosters paternal care (collaboration with C. Pena - Princeton). |
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