Biology subjects

Medeiros, D. M.

Publications and source records attributed to Medeiros, D. M..

4 recordsLinked to original sources

bioRxiv2025

Establishment, conservation, and innovation of dorsal determination mechanisms during the evolution of vertebrate paired appendages

Limb function requires polarized anatomy across the dorsal-ventral (DV) axis, but it is unclear when the capacity for DV differentiation of paired appendages arose in evolution. Here we define ancestral DV patterning programs in the fins of fishes. We show that the orthologue of the limb dorsal determinant, Lmx1b, is required to establish dorsality in zebrafish pectoral fins and is regulated by a conserved LARM cis-regulatory hub. However, lmx1bb expression in median fins is unaffected by removal of the LARM, suggesting its regulation is an evolutionary innovation specific to the paired appendages. Although we find the LARM is highly conserved across gnathostomes, we identify specific alteration of this region in hillstream loaches, fishes which naturally parallel "double-ventral" fin phenotypes observed in lmx1bb and LARM mutants. Altogether our findings indicate LARM-mediated dorsal identity is an ancestral feature of paired appendages that provide a prepattern for limb evolution and lineage diversification.

evolutionary biology↗

bioRxiv2020

Lamprey Lecticans Link New Vertebrate Genes to the Origin and Elaboration of Vertebrate Tissues

The evolution of vertebrates from an invertebrate chordate ancestor involved the evolution of new organs, tissues, and cell types. It was also marked by the origin and duplication of new gene families. If, and how, these morphological and genetic innovations are related is an unresolved question in vertebrate evolution. Hyaluronan is an extracellular matrix (ECM) polysaccharide important for water homeostasis and tissue structure. Vertebrates possess a novel family of hyaluronan binding proteins called Lecticans, and studies in jawed vertebrates (gnathostomes) have shown they function in many of the cells and tissues that are unique to vertebrates. This raises the possibility that the origin and/or expansion of this gene family helped drive the evolution of these vertebrate novelties. In order to better understand the evolution of the lectican gene family, and its role in the evolution of vertebrate morphological novelties, we investigated the phylogeny, genomic arrangement, and expression patterns of all lecticans in the sea lamprey (Petromyzon marinus), a jawless vertebrate. Though both P. marinus and gnathostomes have four lecticans, our phylogenetic and syntenic analyses suggest lamprey lecticans are the result of one or more cyclostome-specific duplications. Despite the independent expansion of the lamprey and gnathostome lectican families, we find highly conserved expression of lecticans in vertebrate-specific and mesenchyme-derived tissues. We also find that, unlike gnathostomes, lamprey expresses its lectican paralogs in distinct subpopulations of head skeleton precursors, potentially reflecting an ancestral diversity of skeletal tissue types. Together, these observations suggest that the ancestral pre-duplication lectican had a complex expression pattern, functioned to support mesenchymal histology, and likely played a role in the evolution of vertebrate-specific cell and tissue types.

evolutionary biology↗

bioRxiv2020

Evolution of vertebrate gill covers via shifts in an ancient Pou3f3 enhancer

Whereas the gill chambers of extant jawless vertebrates (lampreys and hagfish) open directly into the environment, jawed vertebrates evolved skeletal appendages that promote the unidirectional flow of oxygenated water over the gills. A major anatomical difference between the two jawed vertebrate lineages is the presence of a single large gill cover in bony fishes versus separate covers for each gill chamber in cartilaginous fishes. Here we find that these divergent gill cover patterns correlate with the pharyngeal arch expression of Pou3f3 orthologs. We identify a Pou3f3 arch enhancer that is deeply conserved from cartilaginous fish through humans but undetectable in lampreys, with minor sequence differences in the bony versus cartilaginous fish enhancers driving the corresponding single versus multiple gill arch expression patterns. In zebrafish, loss of Pou3f3 gene function disrupts gill cover formation, and forced expression of Pou3f3b in the gill arches generates ectopic skeletal elements resembling the multiple gill cover pattern of cartilaginous fishes. Emergence of this Pou3f3 enhancer >430 mya and subsequent modifications may thus have contributed to the acquisition and diversification of gill covers and respiratory strategies during gnathostome evolution.

developmental biology↗

bioRxiv2019

Cooption and Specialization of Endothelin Signaling Pathways Drove Elaboration of the Neural Crest in Early Vertebrates

The neural crest (NC) is a vertebrate-specific embryonic tissue that forms an array of clade-defining adult features. A key step in the formation of these diverse derivatives is the partitioning of NC cells into subpopulations with distinct migration routes and potencies1. The evolution of these developmental modules is poorly understood. Endothelin (Edn) signaling is unique to vertebrates, and performs various functions in different NC subpopulations2-5. To better understand the evolution of NC patterning, we used CRISPR/Cas9-driven mutagenesis to disrupt Edn receptors, ligands, and Dlx transcription factors in the sea lamprey, Petromyzon marinus. Lampreys and modern gnathostomes last shared a common ancestor 500 million years ago6. Thus, comparisons between the two groups can identify deeply conserved and divergent features of vertebrate development. Using Xenopus laevis to facilitate side-by-side analyses, we show here that lamprey and gnathostomes display fundamental differences in Edn signaling function. Unlike gnathostomes, both lamprey Ednrs cooperate during oropharyngeal skeleton development. Furthermore, neither paralog regulates hand transcription factors, which are required for mandible development in gnathostomes. We also identify conserved roles for Edn signaling in dlx gene regulation, pigment cell, and heart development. Together our results illustrate the stepwise neofunctionalization and specialization of this vertebrate-specific signaling pathway, and suggest key intermediate stages in the early evolution of the NC.

developmental biology↗