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1. Differential Impact of Hoxa11 and Hoxd11 on Pisiform Ossification and Epiphysis Formation

   Graziano, Timothy ; Sweeney, Brendan ; Kjosness, Kelsey M ; Kistler, Sabrina ; Schuetz, Emily ; Thompson, Ryan ; Reno, Philip ( May 2021 , The FASEB journal)

   null (Ed.)

   Hox genes are key developmental patterning genes that impact segmental identity and skeletal patterning. Hox11 genes are known to impact wrist and ankle development and are expressed around the developing pisiform and calcaneus. These paralogous bones in the wrist and ankle are the only carpal and tarsal to form a growth plate in mammals, although humans have lost this growth plate and the associated primary ossification center in the pisiform. Loss-of-function mutations to Hoxa11 and Hoxd11 result in pisiform truncation and appear to also cause at least some disorganization of the growth plate cartilage; however, little is known about the nature of this disorganization or if ossification timing is impacted by Hox11 genes. The present study investigates the role of Hoxa11 and Hoxd11 in pisiform growth plate organization and ossification timing. We conducted histological analysis of the pisiform growth plate in juvenile mice with Hoxa11 and Hoxd11 loss-of-function mutations and compared them to ossification patterns observed in age- and genotype-matched whole-mount specimens that were cleared and stained with Alizarin red and Alcian blue to visualize bone and cartilage, respectively. Histological analysis reveals a dosage-dependent impact of Hox11 mutations on pisiform ossification to both the primary and secondary ossification center. As the number of Hox11 mutation alleles increase, less bone is present in the early primary ossification center compared to age-matched specimens. In specimens with three loss-of-function alleles, no trabeculae or growth plate organization are visible at P9, when both are well established in wild type specimens. Cleared and stained specimens indicate a possible pseudo epiphysis forming with Hoxd11 mutation, while Hoxa11 knockout specimens have not formed any visible epiphysis or calcification by P9. These results indicate that ossification timing and patterns, along with growth plate organization, are affected by Hox11 mutations during early pisiform ossification. Furthermore, Hoxa11 and Hoxd11 alter the pisiform epiphysis differently, suggesting that each plays a specific role in formation of the ossification front and epiphysis ossification either by influencing timing, ossification progression, or both. Further work is needed to understand the mechanisms by which Hox genes impact ossification patterns and timing, as well as the differential roles of Hoxa11 and Hoxd11 in growth plate organization and epiphysis formation. 

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2. Morphological Changes in Calcanei of Mice with Hoxa11 and Hoxd11 loss-of-function mutations

   Goldman, Samuel ; Bhavsar, Avani ; Kjosness, Kelsey M ; Kistler, Sabrina ; Schuetz, Emily ; Stephens, Nicholas ; Ryan, Timothy M ; Reno, Philip L ( May 2021 , The FASEB journal)

   null (Ed.)

   Hox11 genes are expressed around the developing wrist and ankle and are known to substantially impact pisiform shape and length in mice. The calcaneus is a tarsal bone that is paralogous to the pisiform in the wrist, but previous descriptions of mice with Hox11 mutations have suggested that little morphological change takes place unless Hoxa11 and Hoxd11 are both knocked out, at which point the calcaneus fails to form. However, these studies primarily relied on cleared and stained whole-mount specimens which limit resolution of morphological features. This study seeks to determine if calcaneus morphology is altered by three or fewer loss-of-function Hoxa11 and Hoxd11 alleles. We obtained microCT scans of 8 week old mice and compared calcaneus morphology in wild type mice and mice with one, two, and three Hoxa11 and Hoxd11 loss-of-function alleles. We used auto3dgm to conduct a 3D geometric morphometric analysis of shape variation using surface semi-landmarks. Principle components (PC) analysis indicates that calcaneus morphology is altered in mice with Hoxa11 and Hoxd11 loss-of-function mutations. PC1 accounts for 35.4% of shape variation and results from changes to the width and height of the calcaneal neck and shape of peroneal tubercle/process. PC2 accounts for 11.9% of shape variation and results from changes to the width of the calcaneal tuberosity and height of the posterior talar facet. Most specimens with either combination of three out of four Hoxa11 and Hoxd11 loss-of-function alleles cluster together. The other genotypes form a gradient of morphological change with WT, Hoxd11 heterozygotes, and Hoxd11 knockouts being most similar to each other and Hoxa11 heterozygotes, Hoxa11 knockouts, and heterozygotes for both genes being most similar to each other. These results suggest that Hox11 loss-of-function mutations result in altered calcaneus morphology and Hoxa11 and Hoxd11 loss-of-function mutations alter the shape of the calcaneus in different ways when fewer than three alleles are knocked out. 

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3. Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post‐traumatic Osteoarthritis

   https://doi.org/10.1002/art.41254  

   Li, Qing ; Han, Biao ; Wang, Chao ; Tong, Wei ; Wei, Yulong ; Tseng, Wei‐Ju ; Han, Li‐Hsin ; Liu, X. Sherry ; Enomoto‐Iwamoto, Motomi ; Mauck, Robert L. ; et al ( July 2020 , Arthritis & Rheumatology)

   To elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis (OA).

   Three‐month–old decorin‐null (Dcn^−/−) and inducible decorin‐knockout (Dcn^iKO) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post‐traumaticOA. TheOAphenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy–nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro–computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild‐type and Dcn^−/−mice were stimulated with the inflammatory cytokine interleukin‐1β (IL‐1β) in vitro (n = 6 mice per group). The resulting chondrocyte response toIL‐1β and release ofsGAGs were quantified.

   In both Dcn^−/−and Dcn^iKOmice, the absence of decorin resulted in acceleratedsGAGloss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P< 0.05). Also, Dcn^−/−mice developed more salient osteophytes, illustrating more severeOA. In cartilage explants treated withIL‐1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion ofsGAGs was released to the media from Dcn^−/−mouse explants, in both live and devitalized conditions (P< 0.05).

   In post‐traumaticOA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.

    

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4. Ontogenetic transformation of the cartilaginous nasal capsule in mammals, a review with new observations on bats

   https://doi.org/10.1002/ar.25152  

   Smith, Timothy D. ; Ruf, Irina ; DeLeon, Valerie B. ( January 2023 , The Anatomical Record)

   The nasal capsule, as the most rostral part of the chondrocranium, is a critical point of connection with the facial skeleton. Its fate may influence facial form, and the varied fates of cartilage may be a vehicle contributing to morphological diversity. Here, we review ontogenetic changes in the cartilaginous nasal capsule of mammals, and make new observations on perinatal specimens of two chiropteran species of different suborders. Our observations reveal some commonalities betweenRousettus leschenaultiiandDesmodus rotundus, such as perinatal ossification of the first ethmoturbinal. However, inRousettus, ossification of turbinals is demonstrated as either perichondrial or endochondral. InDesmodus, perichondrial and endochondral ossification of the posterior nasal cupula is observed at birth, a part of the nasal capsule previously shown to persist as cartilage into infancy inRousettus. Combined with prior findings on cranial cartilages we identify several diverse transformational mechanisms by which cartilage as a tissue type may contribute to morphological diversity of the cranium. First, cartilage differentiates in an iterative fashion to increase nasal complexity, but still retains the capacity for later elaboration via de novo bone emanating outward before or after cartilage ossifies. Second, cartilage acts as a driver of growth at growth centers, or via interstitial growth (e.g., septal cartilage). Finally, cartilage as a tissue may influence the timing of ossification and union of the facial and basicranial skeleton. In particular, cartilage at certain points of ontogeny may “model” via selective resorption, showing some similarity to bone.

    

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5. Tomato locule number and fruit size controlled by natural alleles of lc and fas

   https://doi.org/10.1002/pld3.142  

   Chu, Yi‐Hsuan ; Jang, Jyan‐Chyun ; Huang, Zejun ; van der Knaap, Esther ( July 2019 , Plant Direct)

   Improving yield by increasing the size of produce is an important selection criterion during the domestication of fruit and vegetable crops. Genes controlling meristem organization and organ formation work in concert to regulate the size of reproductive organs. In tomato,lcandfascontrol locule number, which often leads to enlarged fruits compared to the wild progenitors.LCis encoded by the tomato ortholog ofWUSCHEL(WUS), whereasFASis encoded by the tomato ortholog ofCLAVATA3 (CLV3). The critical role of theWUS‐CLV3 feedback loop in meristem organization has been demonstrated in several plant species. We show that mutant alleles for both loci in tomato led to an expansion of theSlWUSexpression domain in young floral buds 2–3 days after initiation. Single and double mutant alleles oflcandfasmaintain higherSlWUSexpression during the development of the carpel primordia in the floral bud. This augmentation and altered spatial expression ofSlWUSprovided a mechanistic basis for the formation of multilocular and large fruits. Our results indicated thatlcandfasare gain‐of‐function and partially loss‐of‐function alleles, respectively, while both mutations positively affect the size of tomato floral meristems. In addition, expression profiling showed thatlcandfasaffected the expression of several genes in biological processes including those involved in meristem/flower development, patterning, microtubule binding activity, and sterol biosynthesis. Several differentially expressed genes co‐expressed withSlWUShave been identified, and they are enriched for functions in meristem regulation. Our results provide new insights into the transcriptional regulation of genes that modulate meristem maintenance and floral organ determinacy in tomato.

    

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