Amazing stuff!
"... Two independent but complementary studies published today uncover surprising details about the composition of external ears and how they evolved. One study in Science reveals that mammalian outer ears—and other body parts—are rich in an unusual form of cartilage that is packed with lipids and shows increased flexibility.
On the evolutionary front, a paper in Nature finds that the genetic control circuits that shape mammalian external ears may have descended from similar circuits in fish gills. ...
Fish gills and human ear cartilage also share key DNA sequences that boost activity of particular genes, the researchers determined. Five of the 14 sequences they identified in human ear cartilage occurred in zebrafish gill cartilage. But only one was present in nongill cartilage from the fish. The scientists also showed that at least some of these sequences are interchangeable between fish and mammals. ..."
From the editor's summary and abstract (1):
"Editor’s summary
Cartilage is considered to be a mostly cell-free tissue made of copious extracellular matrix. Ramos et al. describe the embryonic development, gene expression, biochemistry, physiology, and biomechanics of lipid-filled cartilage in mice. This “fatty cartilage” forms from lipochondrocytes found in the face, neck, and chest of phylogenetically diverse mammals. It can adopt intricately patterned shapes and has life-long stability and elastic properties because of its large lipid vacuoles within numerous long-lived cells having little extracellular matrix. These findings hold promise for advancing our understanding of form-to-function relationships in skeletal tissues. ...
Structured Abstract
INTRODUCTION
Vertebrates have a complex endoskeleton that consists of cartilage and ossifying bones. The biomechanics of the collagen-rich extracellular matrix in cartilage underlie its physical integrity. Additionally, during embryonic development, vertebrates also form the notochord, an endoskeletal tissue that affords animal bodies with mechanical support through hydrostatics. The notochord maintains its shape and stiffness owing to its large cells, whose aqueous vacuoles resist compression. Remnants of the notochord in most vertebrates became the nucleus pulposus, a ball-like structure at the center of intervertebral disks.
RATIONALE
In this study, we noticed adipocyte-like cells featuring a giant lipid vacuole present throughout mouse ear cartilage. Yet, unlike adipocytes, these cells did not label with adipose-specific genetic markers. We chose to characterize this form of cartilage, called lipocartilage, which we found in vital anatomical structures of the nose, ear, larynx, and chest, and to establish whether its biomechanical properties depend on intracellular vacuoles.
RESULTS
We found that precursor cells for lipocartilage expressed transcriptional factors and extracellular matrix genes shared with the progenitors of “conventional” cartilage. During terminal differentiation, lipocartilage precursor cells activated lipid metabolism genes, including de novo lipogenesis enzymes that convert glucose to fatty acids. Lipocartilage formation depended on de novo lipogenesis to synthesize lipid vacuoles, and unlike adipocytes, its cells could not take up additional fatty acids from the circulation. Furthermore, compared with adipocytes, mature lipocartilage cells lacked enzymes needed to breakdown stored lipids, resulting in metabolically “locked” vacuoles.
In fact, when adult mice were challenged with either caloric restriction or a high-fat diet, their external ears and the lipid vacuoles contained within them did not change in size. This was in contrast to adipose tissues, which readily emptied or filled their lipid vacuoles, respectively.
Beyond rodents, we identified lipocartilage in phylogenetically diverse mammals, including in the ears of echolocating bats, where it becomes particularly intricate. Abundant lipid droplets also form in human cartilage cells grown in vitro from embryonic stem cells.
CONCLUSION
We postulate that lipocartilage is a distinct type of vacuolated skeletal tissue that has evolved in mammals and is similar in form and function to vacuolated notochord.
Lipocartilage attains and maintains its size and shape by adapting a distinct lipid metabolism program that enables the formation of superstable lipid vacuoles. Skeletal elements made of lipocartilage commonly acquire complex, micropatterned shapes, such as in elaborately shaped bat ears. Our lipid washout assays further suggest that vacuoles are critically required for lipocartilage biomechanics, calling for in-depth studies on the structure-function relationship between intracellular vacuoles versus extracellular matrix in skeletal tissues. Regenerative medicine strategies for embryonic stem cell–derived human cartilage can use lipid vacuoles as a natural biomarker that distinguishes differentiated cells from pluripotent progenitors."
From the abstract (2):
"How novel structures emerge during evolution has long fascinated biologists. A dramatic example is how the diminutive bones of the mammalian middle ear arose from ancestral fish jawbones.
In contrast, the evolutionary origin of the outer ear, another mammalian innovation, remains a mystery, in part because it is supported by non-mineralized elastic cartilage rarely recovered in fossils. Whether the outer ear arose de novo or through reuse of ancestral developmental programs is unknown.
Here we show that the outer ear shares gene regulatory programs with the gills of fishes and amphibians for both its initial outgrowth and later development of elastic cartilage. Comparative single-nuclei multiomics of the human outer ear and zebrafish gills reveals conserved gene expression and putative enhancers enriched for common transcription factor binding motifs. This is reflected by transgenic activity of human outer ear enhancers in gills, and fish gill enhancers in the outer ear. Further, single-cell multiomics of the cartilaginous book gills of horseshoe crabs reveal a shared DLX-mediated gill program with vertebrates, with a book gill distalless enhancer driving expression in zebrafish gills. We propose that elements of an invertebrate gill program were reutilized in vertebrates to generate first gills and then the outer ear."
Superstable lipid vacuoles endow cartilage with its shape and biomechanics (no public access)
Repurposing of a gill gene regulatory program for outer ear evolution (no public access)
Lipid-filled cartilage of mammals.
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