The DOI matches its Crossref record.
Hoxa-13 and Hoxd-13 play a crucial role in the patterning of the limb autopod
Abstract
SUMMARY: Members of the Abdominal-B-related Hox gene subfamily (belonging to homology groups 9 to 13) are coordinately expressed during limb bud development. Only two genes from homology group 13 (Hoxa-13 and Hoxd-13) are specifically expressed in the developing distal region (the autopod), which displays the most complex and evolutionarily flexible pattern among limb ‘segments’. We report here that targeted disruption of the Hoxa-13 gene leads to a specific forelimb and hindlimb autopodal phenotype, distinct from that of the Hoxd-13 paralogous gene inactivation. In both limbs, Hoxa-13 loss of function results in the lack of formation of the most anterior digit and to altered morphogenesis of some ‘preaxial’ carpal/tarsal elements. We have generated mice with all possible combinations of disrupted Hoxa-13 and/or Hoxd-13 alleles, which allowed us to investigate the degree of functional specificity versus redundancy of the corresponding gene products in the developing limb autopod. The phenotype of any double mutant was much more severe than the sum of the phenotypes seen in the corresponding single mutants, indicating that these genes act in a partially redundant manner. Our major findings were: (1) an abnormal autopodal phenotype in Hoxa-13+/−/Hoxd-13+/− double heterozygous mutants, which mostly consists of subsets of the alterations seen in each individual homozygous mutant, and therefore appears to result from quantitative, rather than qualitative, homeoprotein deficiency; (2) partly distinct alterations in mutants harboring a single non-disrupted allele of Hoxa-13 or Hoxd-13, indicating that the remaining reduced protein amounts are not functionally equivalent; (3) a polydactyly in the forelimbs of Hoxa-13+/−/Hoxd-13−/− double mutants, consisting of seven symmetrically arranged, truncated and mostly non-segmented digits; (4) an almost complete lack of chondrified condensations in the autopods of double homozygous mutants, showing that the activity of group 13 Hox gene products is essential for autopodal patterning in tetrapod limbs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Diversity, topographic differentiation, and positional memory in human fibroblasts
Chang, H. Y., Chi, J.-T., Dudoit, S., Bondre, C., van de Rijn, M., Botstein, D., & Brown, P. O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162488599 · Cited by 1,151
Cells keep a memory of their tissue origin during axolotl limb regeneration
Kragl, M., Knapp, D., Nacu, E., Khattak, S., Maden, M., Epperlein, H. H., & Tanaka, E. M. (2009) · Nature · doi:10.1038/nature08152 · Cited by 850
Development of the Endochondral Skeleton
Long, F., & Ornitz, D. M. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008334 · Cited by 663
Hox10 and Hox11 Genes Are Required to Globally Pattern the Mammalian Skeleton
Wellik, D. M., & Capecchi, M. R. (2003) · Science · doi:10.1126/science.1085672 · Cited by 586
Molecular Models for Vertebrate Limb Development
Johnson, R. L., & Tabin, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80364-5 · Cited by 580
A Global Control Region Defines a Chromosomal Regulatory Landscape Containing the HoxD Cluster
Spitz, F., Gonzalez, F., & Duboule, D. (2003) · Cell · doi:10.1016/s0092-8674(03)00310-6 · Cited by 472
Quagliata, L., Matter, M. S., Piscuoglio, S., Arabi, L., Ruiz, C., Procino, A., Kovac, M., Moretti, F., Makowska, Z., Boldanova, T., et al. (2014) · Hepatology · doi:10.1002/hep.26740 · Cited by 434
Interpreting the posture and locomotion ofAustralopithecus afarensis: Where do we stand?
Ward, C. V. (2002) · American Journal of Physical Anthropology · doi:10.1002/ajpa.10185 · Cited by 364
Warot, X., Fromental-Ramain, C., Fraulob, V., Chambon, P., & Dollé, P. (1997) · Development · doi:10.1242/dev.124.23.4781 · Cited by 358
Self-citationHomeobox Genes in Embryogenesis and Pathogenesis
Mark, M., Rijli, F. M., & Chambon, P. (1997) · Pediatric Research · doi:10.1203/00006450-199710000-00001 · Cited by 318
Self-citationPlzf regulates limb and axial skeletal patterning
Barna, M., Hawe, N., Niswander, L., & Pandolfi, P. P. (2000) · Nature Genetics · doi:10.1038/76014 · Cited by 279
Galli, A., Robay, D., Osterwalder, M., Bao, X., Bénazet, J.-D., Tariq, M., Paro, R., Mackem, S., & Zeller, R. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000901 · Cited by 269
The development of the paired fins in the zebrafish (Danio rerio).
Grandel, H., & Schulte-Merker, S. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(98)00176-2 · Cited by 267
Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function
Kmita, M., Tarchini, B., Zàkàny, J., Logan, M., Tabin, C. J., & Duboule, D. (2005) · Nature · doi:10.1038/nature03648 · Cited by 262
Chapter 9 Hox Genes and Vertebrate Axial Pattern
Wellik, D. M. (2009) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(09)88009-5 · Cited by 203
Hox genes in digit development and evolution
Zákány, J., & Duboule, D. (1999) · Cell and Tissue Research · doi:10.1007/s004410051262 · Cited by 178
Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling
Suzuki, T., Takeuchi, J., Koshiba-Takeuchi, K., & Ogura, T. (2004) · Developmental Cell · doi:10.1016/s1534-5807(03)00401-5 · Cited by 148
A human embryonic limb cell atlas resolved in space and time
Zhang, B., He, P., Lawrence, J. E. G., Wang, S., Tuck, E., Williams, B. A., Roberts, K., Kleshchevnikov, V., Mamanova, L., Bolt, L., et al. (2024) · Nature · doi:10.1038/s41586-023-06806-x · Cited by 143
The origin of digits: Expression patterns versus regulatory mechanisms
Woltering, J. M., & Duboule, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.04.002 · Cited by 125
Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci
Lonfat, N., Montavon, T., Darbellay, F., Gitto, S., & Duboule, D. (2014) · Science · doi:10.1126/science.1257493 · Cited by 113
Cobb, J., & Duboule, D. (2005) · Development · doi:10.1242/dev.01885 · Cited by 104
Latent developmental potential to form limb-like skeletal structures in zebrafish
Hawkins, M. B., Henke, K., & Harris, M. P. (2021) · Cell · doi:10.1016/j.cell.2021.01.003 · Cited by 80
The little skate genome and the evolutionary emergence of wing-like fins
Marlétaz, F., de la Calle-Mustienes, E., Acemel, R. D., Paliou, C., Naranjo, S., Martínez-García, P. M., Cases, I., Sleight, V. A., Hirschberger, C., Marcet-Houben, M., et al. (2023) · Nature · doi:10.1038/s41586-023-05868-1 · Cited by 71
Roscito, J. G., Sameith, K., Kirilenko, B. M., Hecker, N., Winkler, S., Dahl, A., Rodrigues, M. T., & Hiller, M. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110280 · Cited by 44
Hérault, Y., Beckers, J., Kondo, T., Fraudeau, N., & Duboule, D. (1998) · Development · doi:10.1242/dev.125.9.1669 · Cited by 35
Zhou, W., Zhu, H., Zhao, J., Li, H., Wan, Y., Cao, J., Zhao, H., Yu, J., Zhou, R., Yao, Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064237 · Cited by 13
Delgado, I., Domínguez‐Frutos, E., Schimmang, T., & Ros, M. A. (2008) · Developmental Dynamics · doi:10.1002/dvdy.21452 · Cited by 13
Metadata
- Authors
- Fromental-Ramaint, C., Warott, X., Messadecq, N., LeMeur, M., Dolle, P., & Chambon, P.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1995-02-01
- Volume
- 122
- Issue
- 10
- Pages
- 2997-3011
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2150080189
- Cited by
- 436
- References
- 0
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
