Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage
Limb patterning relies in large part on the function of the <i>Hox</i> family of developmental genes. While the differential expression of <i>Hox</i> genes shifts from the anterior–posterior (A–P) to the proximal–distal (P–D) axis around embryonic day 11 (E11), whether this s...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Journal of Developmental Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2221-3759/8/4/31 |
| _version_ | 1797545434122551296 |
|---|---|
| author | Ines Desanlis Rachel Paul Marie Kmita |
| author_facet | Ines Desanlis Rachel Paul Marie Kmita |
| author_sort | Ines Desanlis |
| collection | DOAJ |
| description | Limb patterning relies in large part on the function of the <i>Hox</i> family of developmental genes. While the differential expression of <i>Hox</i> genes shifts from the anterior–posterior (A–P) to the proximal–distal (P–D) axis around embryonic day 11 (E11), whether this shift coincides with a more global change of A–P to P–D patterning program remains unclear. By performing and analyzing the transcriptome of the developing limb bud from E10.5 to E12.5, at single-cell resolution, we have uncovered transcriptional trajectories that revealed a general switch from A–P to P–D genetic program between E10.5 and E11.5. Interestingly, all the transcriptional trajectories at E10.5 end with cells expressing either proximal or distal markers suggesting a progressive acquisition of P–D identity. Moreover, we identified three categories of genes expressed in the distal limb mesenchyme characterized by distinct temporal expression dynamics. Among these are <i>Hoxa13</i> and <i>Hoxd13</i> (<i>Hox13</i> hereafter), which start to be expressed around E10.5, and importantly the binding of the HOX13 factors was observed within or in the neighborhood of several of the distal limb genes. Our data are consistent with previous evidence suggesting that the transition from the early/proximal to the late/distal transcriptome of the limb mesenchyme largely relies on HOX13 function. Based on these results and the evidence that HOX13 factors restrict <i>Hoxa11</i> expression to the proximal limb, in progenitor cells of the zeugopod, we propose that HOX13 act as a key determinant of P–D patterning. |
| first_indexed | 2024-03-10T14:16:19Z |
| format | Article |
| id | doaj.art-2ede7bbd6d8a4abf8839df021b916b69 |
| institution | Directory Open Access Journal |
| issn | 2221-3759 |
| language | English |
| last_indexed | 2024-03-10T14:16:19Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Developmental Biology |
| spelling | doaj.art-2ede7bbd6d8a4abf8839df021b916b692023-11-20T23:46:46ZengMDPI AGJournal of Developmental Biology2221-37592020-12-01843110.3390/jdb8040031Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud StageInes Desanlis0Rachel Paul1Marie Kmita2Genetics and Development Research Unit, Institut de Recherches Cliniques de Montréal, Montreal, QC H2W 1R7, CanadaGenetics and Development Research Unit, Institut de Recherches Cliniques de Montréal, Montreal, QC H2W 1R7, CanadaGenetics and Development Research Unit, Institut de Recherches Cliniques de Montréal, Montreal, QC H2W 1R7, CanadaLimb patterning relies in large part on the function of the <i>Hox</i> family of developmental genes. While the differential expression of <i>Hox</i> genes shifts from the anterior–posterior (A–P) to the proximal–distal (P–D) axis around embryonic day 11 (E11), whether this shift coincides with a more global change of A–P to P–D patterning program remains unclear. By performing and analyzing the transcriptome of the developing limb bud from E10.5 to E12.5, at single-cell resolution, we have uncovered transcriptional trajectories that revealed a general switch from A–P to P–D genetic program between E10.5 and E11.5. Interestingly, all the transcriptional trajectories at E10.5 end with cells expressing either proximal or distal markers suggesting a progressive acquisition of P–D identity. Moreover, we identified three categories of genes expressed in the distal limb mesenchyme characterized by distinct temporal expression dynamics. Among these are <i>Hoxa13</i> and <i>Hoxd13</i> (<i>Hox13</i> hereafter), which start to be expressed around E10.5, and importantly the binding of the HOX13 factors was observed within or in the neighborhood of several of the distal limb genes. Our data are consistent with previous evidence suggesting that the transition from the early/proximal to the late/distal transcriptome of the limb mesenchyme largely relies on HOX13 function. Based on these results and the evidence that HOX13 factors restrict <i>Hoxa11</i> expression to the proximal limb, in progenitor cells of the zeugopod, we propose that HOX13 act as a key determinant of P–D patterning.https://www.mdpi.com/2221-3759/8/4/31limb patterningsingle-cell RNA-seq<i>Hox</i> genes |
| spellingShingle | Ines Desanlis Rachel Paul Marie Kmita Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage Journal of Developmental Biology limb patterning single-cell RNA-seq <i>Hox</i> genes |
| title | Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage |
| title_full | Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage |
| title_fullStr | Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage |
| title_full_unstemmed | Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage |
| title_short | Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage |
| title_sort | transcriptional trajectories in mouse limb buds reveal the transition from anterior posterior to proximal distal patterning at early limb bud stage |
| topic | limb patterning single-cell RNA-seq <i>Hox</i> genes |
| url | https://www.mdpi.com/2221-3759/8/4/31 |
| work_keys_str_mv | AT inesdesanlis transcriptionaltrajectoriesinmouselimbbudsrevealthetransitionfromanteriorposteriortoproximaldistalpatterningatearlylimbbudstage AT rachelpaul transcriptionaltrajectoriesinmouselimbbudsrevealthetransitionfromanteriorposteriortoproximaldistalpatterningatearlylimbbudstage AT mariekmita transcriptionaltrajectoriesinmouselimbbudsrevealthetransitionfromanteriorposteriortoproximaldistalpatterningatearlylimbbudstage |