An official website of the United States government
Abstract The avian transition from long to short, distally fused tails during the Mesozoic ushered in the Pygostylian group, which includes modern birds. The avian tail embodies a bipartite anatomy, with the proximal separate caudal vertebrae region, and the distal pygostyle, formed by vertebral fusion. This study investigates developmental features of the two tail domains in different bird groups, and analyzes them in reference to evolutionary origins. We first defined the early developmental boundary between the two tail halves in the chicken, then followed major developmental structures from early embryo to post-hatching stages. Differences between regions were observed in sclerotome anterior/posterior polarity and peripheral nervous system development, and these were consistent in other neognathous birds. However, in the paleognathous emu, the neognathous pattern was not observed, such that spinal nerve development extends through the pygostyle region. Disparities between the neognaths and paleognaths studied were also reflected in the morphology of their pygostyles. The ancestral long-tailed spinal nerve configuration was hypothesized from brown anole and alligator, which unexpectedly more resembles the neognathous birds. This study shows that tail anatomy is not universal in avians, and suggests several possible scenarios regarding bird evolution, including an independent paleognathous long-tailed ancestor.
more »
« less
Nonpathological inflammation drives the development of an avian flight adaptation
The development of modern birds provides a window into the biology of their dinosaur ancestors. We investigated avian postnatal development and found that sterile inflammation drives formation of the pygostyle, a compound structure resulting from bone fusion in the tail. Inflammation is generally induced by compromised tissue integrity, but here is involved in normal bone development. Transcriptome profiling and immuno/histochemistry reveal a robust inflammatory response that resembles bone fracture healing. The data suggest the involvement of necroptosis and multiple immune cell types, notably heterophils (the avian equivalent of neutrophils). Additionally, nucleus pulposus structures, heretofore unknown in birds, are involved in disc remodeling. Anti-inflammatory corticosteroid treatment inhibited vertebral fusion, substantiating the crucial role of inflammation in the ankylosis process. This study shows that inflammation can drive developmental skeletogenesis, in this case leading to the formation of a flight-adapted tail structure on the evolutionary path to modern avians.
more »
« less
- Award ID(s):
- 2229308
- PAR ID:
- 10573830
- Editor(s):
- Tabin, Cliff
- Publisher / Repository:
- National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 120
- Issue:
- 19
- ISSN:
- 0027-8424
- Subject(s) / Keyword(s):
- intervertebral disc nucleus pulposus necroptosis heterophil corticosteroid
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Proteoglycans are core proteins associated with carbohydrate/sugar moieties that are highly variable in disaccharide composition, which dictates their function. These carbohydrates are named glycosaminoglycans, and they can be attached to proteoglycans or found free in tissues or on cell surfaces. Glycosaminoglycans such as hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparin/heparan sulfate have multiple functions including involvement in inflammation, immunity and connective tissue structure, and integrity. Heparan sulfate is a highly sulfated polysaccharide that is abundant in the periodontium including alveolar bone. Recent evidence supports the contention that heparan sulfate is an important player in modulating interactions between damage associated molecular patterns and inflammatory receptors expressed by various cell types. The structure of heparan sulfate is reported to dictate its function, thus, the utilization of a homogenous and structurally defined heparan sulfate polysaccharide for modulation of cell function offers therapeutic potential. Recently, a chemoenzymatic approach was developed to allow production of many structurally defined heparan sulfate carbohydrates. These oligosaccharides have been studied in various pathological inflammatory conditions to better understand their function and their potential application in promoting tissue homeostasis. We have observed that specific size and sulfation patterns can modulate inflammation and promote tissue maintenance including an anabolic effect in alveolar bone. Thus, new evidence provides a strong impetus to explore heparan sulfate as a potential novel therapeutic agent to treat periodontitis, support alveolar bone maintenance, and promote bone formation.more » « less
-
To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.more » « less
-
:Diabetes has been linked to an increased risk of mild cognitive impairment (MCI), a conditioncharacterized by a subtle cognitive decline that may precede the development of dementia. Theunderlying mechanisms connecting diabetes and MCI involve complex interactions between metabolicdysregulation, inflammation, and neurodegeneration. A critical mechanism implicated in diabetes andMCI is the activation of inflammatory pathways. Chronic low-grade inflammation, as observed in diabetes,can lead to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha(TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and interferon-gamma (IFNγ), each of whichcan exacerbate neuroinflammation and contribute to cognitive decline. A crucial enzyme involved inregulating inflammation is ADAM17, a disintegrin, and metalloproteinase, which can cleave and releaseTNF-α from its membrane-bound precursor and cause it to become activated. These processes, inturn, activate additional inflammation-related pathways, such as AKT, NF-κB, NLP3, MAPK, andJAK-STAT pathways. Recent research has provided novel insights into the role of ADAM17 in diabetesand neurodegenerative diseases. ADAM17 is upregulated in both diabetes and Alzheimer's disease,suggesting a shared mechanism and implicating inflammation as a possible contributor to muchbroader forms of pathology and pointing to a possible link between inflammation and the emergenceof MCI. This review provides an overview of the different roles of ADAM17 in diabetes-associatedmild cognitive impairment diseases. It identifies mechanistic connections through which ADAM17and associated pathways may influence the emergence of mild cognitive impairment.more » « less
-
Amniote skulls are diverse in shape and skeletal composition, which is the basis of much adaptive diversification within this clade. Major differences in skull shape are established early in development, at a critical developmental interval spanning the initial outgrowth and fusion of the facial processes. In birds, this is orchestrated by domains of Shh and Fgf8 expression, known as the frontonasal ectodermal zone (FEZ). It is unclear whether this model of facial development applies to species with diverse facial skeletons, especially species possessing a skull morphology representative of early amniotes. By investigating facial morphogenesis in the lizard, Anolis sagrei, we show that reptilian skull development is driven by the same genes as mammals and birds, but the manner in which those genes regulate facial development is clade-specific. These genes are not expressed in the frontal-nasal prominence, the region of the avian FEZ. Downregulating Shh and Fgf8 signaling disrupts normal facial development, but in pathway-specific ways. Our results demonstrate that early facial morphogenesis in lizards does not conform to the FEZ model. Lizard skull development may be more representative of the ancestral amniote than other model species with highly derived facial skeletons suggesting that the FEZ may be an avian-specific novelty.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1073/pnas.2219757120
