skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


This content will become publicly available on March 15, 2026

Title: The role of the PTHrP /Ihh feedback loop in the unusual growth plate location in mammalian metatarsals and pisiforms
Abstract BackgroundLongitudinal skeletal growth takes place in the cartilaginous growth plates. While growth plates are found at either end of conventional long bones, they occur at a variety of locations in the mammalian skeleton. For example, the metacarpals and metatarsals (MT) in the hands and feet form only a single growth plate at one end, and the pisiform in the wrist is the only carpal bone to contain a growth plate. We take advantage of this natural anatomical variation to test which components of the PTHrP/Ihh feedback loop, a fundamental regulator of chondrocyte differentiation, are specific to growth plate function. ResultsParathyroid hormone‐like hormone(Pthlh), the gene that transcribes parathyroid hormone‐related peptide (PTHrP), is expressed in the reserve zone of the growth plate‐forming end of the MT. At the opposite end, the absence of a PTHrP+ reserve zone results in premature chondrocyte differentiation andIndian hedgehog(Ihh) expression.Pthlhis expressed in the reserve zone of the developing pisiform, confirming the existence of a true growth plate. ConclusionA pool of PTHrP+ reserve zone chondrocytes is a defining characteristic of growth plates, and its patterning may be key to evolved differences in growth plate location in the mammalian skeleton.  more » « less
Award ID(s):
1638812 1656315
PAR ID:
10609163
Author(s) / Creator(s):
; ; ; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Developmental Dynamics
ISSN:
1058-8388
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; (, The FASEB journal)
    null (Ed.)
    Hox genes are key developmental patterning genes that impact segmental identity and skeletal patterning. While Hox11 genes are known to be expressed around the developing calcaneus bone of the ankle, previous studies on mice with Hox11 mutations have indicated that calcaneus morphology is not affected until both Hoxa11 and Hoxd11are knocked out, at which point the calcaneus and talus fail to form.The pisiform bone, a wrist bone that is paralogous to the calcaneus, exhibits substantial morphological and growth plate alterations with Hox11 mutations. We have previously shown that some length differences are present in the adult calcanei of mice with Hoxa11 and Hoxd11 loss-of-function mutations. The present study investigates whether or not the calcaneus growth plate is altered by Hoxa11 and Hoxd11 loss-of-function mutation. We conducted histological analysis of the calcaneus growth plate in juvenile mice with Hoxa11 and Hoxd11 loss-of-function mutations and compared them to ossification patterns observed in whole-mount specimens that were cleared and stained with alizarin red and alcian blue to visualize bone and cartilage, respectively. Histological analysis reveals that early calcaneus growth plates preserve the hypertrophic and proliferative growth plate zones. This is in contrast to the pisiform and likely a result of Hoxc gene expression in the hind limb but not the forelimb. The shape of the epiphyseal cartilage, however, differs greatly in mice with a combined three loss-of-function alleles between Hoxa11 and Hoxd11. In these mice, the calcaneus epiphyseal cartilage is conical shaped with an elongated region of reserve zone chondrocytes. The ossification front and calcaneal tendon insertion are also altered compared to wild type specimens. The first evidence of calcaneal epiphysis ossification appears at P9 in some Hox11 mutant mice, while it typically appears at P11 in wild type specimens. By P17, the epiphysis appears to be larger in specimens with both Hoxa11 and Hoxd11 mutations compared to wild type. These results indicate that the calcaneus growth plate is more resilient to Hox11 mutations than the pisiform, but that the calcaneus exhibits morphological changes and evidence of altered ossification timing with fewer loss-of-function alleles than identified by previous studies. 
    more » « less
  2. ; ; ; ; ; ; (, 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. 
    more » « less
  3. ; ; (, The Anatomical Record)
    Abstract Two‐toed (Choloepus sp.) and three‐toed (Bradypus sp.) sloths possess short, rounded pisiforms that are rare among mammals and differ from other members of Xenarthra like the giant anteater (Myrmecophaga tridactyla) which retain elongated, rod‐like pisiforms in common with most mammals. Using photographs, radiographs, and μCT, we assessed ossification patterns in the pisiform and the paralogous tarsal, the calcaneus, for two‐toed sloths, three‐toed sloths, and giant anteaters to determine the process by which pisiform reduction occurs in sloths and compare it to other previously studied examples of pisiform reduction in humans and orangutans. Both extant sloth genera achieve pisiform reduction through the loss of a secondary ossification center and the likely disruption of the associated growth plate based on an unusually porous subchondral surface. This represents a third unique mechanism of pisiform reduction among mammals, along with primary ossification center loss in humans and retention of two ossification centers with likely reduced growth periods in orangutans. Given the remarkable similarities between two‐toed and three‐toed sloth pisiform ossification patterns and the presence of pisiform reduction in fossil sloths, extant sloth pisiform morphology does not appear to represent a recent convergent adaptation to suspensory locomotion, but instead is likely to be an ancestral trait of Folivora that emerged early in the radiation of extant and fossil sloths. 
    more » « less
  4. ; ; ; ; ; ; (, Cytoskeleton)
    ABSTRACT Of the 61 kinesins annotated inArabidopsis thaliana, many are still without assigned function. Here, we have screened an insertional mutant library of Arabidopsis pollen‐expressed kinesins for fertility defects. Insertional mutants for three kinesins showed a significant reduction in seed set. Among them, we focused on the sole kinesin‐4 expressed in pollen (kinesin‐4C, here Pollen‐Expressed Kinesin 14, PEK14). We show a seed‐set defect in the three independent allelespek14‐1, pek14‐2, and pek14‐3. This defect is male‐derived and is equally distributed throughout the silique. Maturepek14‐1anthers contain about 10% inviable pollen grains.pek14‐1pollen tubes grow 20% more slowly and show reduced pollen tube bending. Analysis of the male germ unit (MGU), as it travels through the pollen tube, demonstrates an aberrant organization of thepek14‐1MGU in 30% of pollen tubes and an increase in the distance of the MGU to the tip by 24%. Expression of GFP‐tagged PEK14 successfully complemented the observed seed set defect, as well as the growth rate, bending, and MGU organization defects observed inpek14‐1. In pollen, PEK14‐GFP is located diffusely at the pollen tube tip. PEK14‐GFP is also expressed in the root meristematic zone and is located at the mid‐zone of the phragmoplast, but no apparent root growth phenotype was observed, likely due to redundancy in this organ. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; ; et al (, Frontiers in Plant Science)
    IntroductionDuring proliferative plant cell division, the new cell wall, called the cell plate, is first built in the middle of the cell and then expands outward to complete cytokinesis. This dynamic process requires coordinated movement and arrangement of the cytoskeleton and organelles. MethodsHere we use live-cell markers to track the dynamic reorganization of microtubules, nuclei, endoplasmic reticulum, and endomembrane compartments during division and the formation of the cell plate in maize leaf epidermal cells. ResultsThe microtubule plus-end localized protein END BINDING1 (EB1) highlighted increasing microtubule dynamicity during mitosis to support rapid changes in microtubule structures. The localization of the cell-plate specific syntaxin KNOLLE, several RAB-GTPases, as well as two plasma membrane localized proteins was assessed after treatment with the cytokinesis-specific callose-deposition inhibitor Endosidin7 (ES7) and the microtubule-disrupting herbicide chlorpropham (CIPC). While ES7 caused cell plate defects inArabidopsis thaliana, it did not alter callose accumulation, or disrupt cell plate formation in maize. In contrast, CIPC treatment of maize epidermal cells occasionally produced irregular cell plates that split or fragmented, but did not otherwise disrupt the accumulation of cell-plate localized proteins. DiscussionTogether, these markers provide a robust suite of tools to examine subcellular trafficking and organellar organization during mitosis and cell plate formation in maize. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email