Dataset Information

Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage.

ABSTRACT: Limb patterning relies in large part on the function of the Hox family of developmental genes. While the differential expression of Hox 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 Hoxa13 and Hoxd13 (Hox13 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 Hoxa11 expression to the proximal limb, in progenitor cells of the zeugopod, we propose that HOX13 act as a key determinant of P-D patterning.

SUBMITTER: Desanlis I

PROVIDER: S-EPMC7768367 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage.

Desanlis Ines I Paul Rachel R Kmita Marie M

Journal of developmental biology 20201207 4

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 unco ...[more]

PMID: 33297480

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Project description:High tibial osteotomy is a common procedure to address unicompartment knee osteoarthritis and other conditions. Regarding the specific surgical methods, medial open wedge osteotomy and lateral close wedge osteotomy are the most used. Both methods have a common disadvantage in that they are not so suitable to correct a severe deformity. Thus, we would like to introduce an anterior proximal-to-posterior distal oblique proximal tibial osteotomy technique, which is especially suitable to correct severe tibial deformity. The most critical point of this technique is to create an osteotomy plane from the most proximal posterior site of the tibial tubercle posteriorly and distally to the posterior cortex of the tibia, with each horizontal osteotomy maneuver in the coronal plane. Combined fibular osteotomy is always needed, and better results can be obtained when it is combined with arthroscopic debridement of the knee. We consider the introduction of this technique will provide a useful option when tibial osteotomy is needed to preserve the knee, especially for a great deformity correction. Technique Video Video 1 Anterior proximal-to-posterior distal oblique proximal tibial osteotomy. This procedure is performed in the right knee. Arthroscopy is performed to confirm the osteoarthritis status of the medial compartment and the healthier status of the lateral compartment. Debridement and other indicated arthroscopic procedures are performed. A K-wire is drilled in the coronal plane from the medial to the lateral side of the tibia at a level approximately 1 cm distal to the joint line, parallels the joint line as far as possible, and is used as a proximal reference wire. Another K-wire is drilled into the tibia also in the coronal plane at a level in the distal one third of the leg and used as a distal reference wire. The angle between the 2 reference wires is controlled being equal to the to-be-corrected angle of the tibia as far as possible. A longitudinal incision is made over the midline of the medial surface of the tibia. The pes anserinus is peeled off from its tibial insertion. A K-wire is placed at the most proximal and posterior site of the tibial tubercle and an osteotomy line is marked posterodistally to the posteromedial ridge of the tibia with 30° angulation to the tibial axis. The posterior osteofascial compartments are opened at the distal end of the osteotomy line. A 2.5-mm K-wire is used to drill through the medial tibial cortex along the osteotomy line to make a line of holes with approximately 5 mm distance between the neighboring holes. An osteotome is used to cut the bone and connect the holes along the osteotomy line at the medial side of the tibia. The lateral tibial cortex is drilled through the medial tibial fissure with each drilling maneuver along the coronal plane, to create a line of holes on the lateral side of the tibia. The osteotome is put into the fissure at the medial side of the tibia to connect the holes on the lateral side of the tibia to create an osteotomy plane. The distal posterior tibial cortex is cut along the osteotomy plane. A K-wire is drilled perpendicular to the coronal plane through the middle of the osteotomy plane. A fibula osteotomy is performed at its middle point with a wire saw. Valgus stress is applied to correct the varus deformity of the tibia till the 2 reference wires parallel to each other. Two additional K-wires are placed across the osteotomy plane for temporary fixation of the fracture. A tibial condyle plate is placed at the medial side of the tibia. Four self-locking screws are placed in respectively at the proximal and distal segments of the tibia for fracture fixation. The K wires for temporary fixation and correction reference are removed. A suction drainage tube is placed to the osteotomy site. The wounds are closed.

Dataset Information

Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage.

Publications

Transcriptional Trajectories in Mouse Limb Buds Reveal the Transition from Anterior-Posterior to Proximal-Distal Patterning at Early Limb Bud Stage.

Similar Datasets

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