Focus

Research

The Mallarino lab is broadly interested in addressing two questions: (1) what are the genetic and developmental mechanisms by which form and structure are regulated during vertebrate embryogenesis? and (2) how are these processes modified during evolutionary time to produce the spectacular phenotypic diversity seen in nature?

We combine the study of non-traditional model organisms, because of their diverse and ecologically relevant phenotypes, with traditional model species, because of the powerful molecular and genetic tools available, to explore questions relating to patterning and evolution of novelty in the mammalian skin. The skin is a powerful model because it exhibits remarkable diversity in form and structure across mammals, is experimentally accessible/tractable, and the molecular mechanisms underlying its formation have been well characterized. We use a variety of approaches, including experimental embryology, genetics, genomics, imaging, and mathematical modelling to uncover gene function and understand mechanisms of evolutionary change. The lab is currently focusing on two model systems: striped rodents and gliding mammals.

Striped rodents

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.

Specific projects: 

Spatial control of genes implementing stripe patterns

Previous work identified the mechanisms by which several genes produce stripes (Mallarino et al. 2016, Nature), but not the mechanisms directly controlling their spatial expression. We are interested in using epigenomic profiling coupled to enhancer screens and functional assays to identify the regulatory mechanisms underlying localized differences in hair color.

Molecular mechanisms of pigment pattern specification

In addition to the direct regulation of pattern implementation genes, we want to uncover the positional signals and upstream cues that establish the pattern itself early in development. We use RNA-sequencing and forward-genetic screens coupled to skin grafts/explant cultures to dissect the detailed temporal and spatial molecular events leading to pigment pattern formation.

Comparative genomics and evolution of pigment patterns

Periodic patterns have evolved in members of at least five different rodent families, with the majority of the diversity concentrated in the Muridae (mice) and the Sciuridae (squirrels). Interestingly, there are several instances in which the same pattern evolved independently in different species. We take a comparative genomics approach to uncover features unique to species with periodic patterns, determine whether the specific organization (i.e., sequence and/or number) of striped phenotypes is constrained by developmental and/or phylogenetic processes, and establish whether the same loci have been repeatedly used by different groups to generate similar outcomes.

Gliding mammals

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. Since dorsal and ventral skin arises from different pools of progenitor cells in the developing embryo, there is a very precise spatial and temporal coordination of the 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 interested in studying the genomic and developmental mechanisms of gliding membrane formation in sugar gliders and flying squirrels to understand how novel structures originate.  

Specific projects: 

Developmental mechanisms of gliding membrane formation

We use RNA-sequencing coupled to functional experiments to understand the mechanisms that direct the growth of the gliding membrane. 

Comparative genomics of gliding

Gliding membranes have independently evolved in different mammalian lineages, from marsupials to placental mammals. A comparative morphological analysis shows that although these membranes resemble one another and serve the same function, they display considerable morphological variation across different species. We take a comparative genomics approach to uncover genetic elements that are common to gliding mammals and those that are unique to the different lineages.

Biography

Ricardo Mallarino is an Assistant Professor of Molecular Biology at Princeton University. Originally from Bogota, Colombia, he graduated with a B.S. in Biology from Universidad de los Andes. He completed his graduate studies at Harvard in Organismic and Evolutionary Biology in 2011, working with Arhat Abzhanov on developmental mechanisms underlying beak shape diversity in Darwin’s finches and their close relatives. After completing his PhD. he joined Hopi Hoekstra’s lab at Harvard, where he established a new model species and developed tools for studying the molecular basis of pigment pattern formation in mammals. Dr. Mallarino’s research focuses on understanding the genetic and developmental mechanisms by which form and structure are regulated during vertebrate embryogenesis and elucidating how these processes get modified during evolutionary time to produce phenotypic diversity.

Honors & Awards