Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

Costa, Emanuel Cura; Otsuki, Leo; Albors, Aida Rodrigo; Tanaka, Elly M.; Chara, Osvaldo

doi:10.7554/elife.55665

Cited by 32 publications

(51 citation statements)

References 52 publications

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“…ST and SV lengths are highly correlated (Pearson coefficient r = 0.9937, P = 3.1 Â 10 À209 , Figure 1A) and their normograms presented a similar trend: a rapid growth phase followed by a slower growth phase (Figure 1B,C, dots). To test whether there is a transition between two subsequent growth modes, we followed a previously reported approach 19,20 to determine the border separating two spatial regions within the anterior-posterior axis of the axolotl spinal cord during regeneration (see Experimental and modelling procedures section). We fitted the ST and SV normograms with a two-line mathematical model, assuming two subsequent linear growths separated by a transition age (Figure 1B,C, continuous line).…”

Section: Resultsmentioning

confidence: 99%

Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum

Riquelme-Guzmán

Schuez

Böhm

et al. 2021

Developmental Dynamics

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Background:The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging. Results:The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to L-thyroxine, increasing the rate of bone formation. Conclusions:In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.

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Section: Resultsmentioning

confidence: 99%

Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum

Riquelme-Guzmán

Schuez

Böhm

et al. 2021

Developmental Dynamics

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“…About 50% of the foxm1 + cells are in S phase and 40% in G2/M, leaving only about 10% of cells in G1. Interestingly, similar changes in cell cycle have been observed in Axolotls, suggesting that changes in cell cycle dynamics may be a general principle of spinal cord regeneration (Rodrigo Albors et al , 2015; Cura Costa et al , 2021). The high proportion of cells in S phase could be due to a synchronised cell cycle as suggested in Axolotl (Cura Costa et al , 2021) or an extension of the relative length of S phase.…”

Section: Discussionmentioning

confidence: 71%

“…ROS are upstream of different signalling pathways, including FGF (Lin & Slack, 2008 ; Love et al , 2013 ). Furthermore, Sonic hedgehog (Shh) signalling is also required for tail regeneration (Beck et al , 2003 ; Hamilton et al , 2021 ) and induces Foxm1 expression in the developing cerebellar granule neuron precursors (Schüller et al , 2007 ). However, foxm1 expression is not affected by treating amputated tails treated with an FGF receptor kinase inhibitor (SU5402, Fig EV1H ) or a Shh signalling inhibitor (cyclopamine, Fig EV1I ).…”

Section: Resultsmentioning

confidence: 99%

Foxm1 regulates neural progenitor fate during spinal cord regeneration

et al. 2021

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Xenopus tadpoles have the ability to regenerate their tails upon amputation. Although some of the molecular and cellular mechanisms that globally regulate tail regeneration have been characterised, tissue‐specific response to injury remains poorly understood. Using a combination of bulk and single‐cell RNA sequencing on isolated spinal cords before and after amputation, we identify a number of genes specifically expressed in the spinal cord during regeneration. We show that Foxm1, a transcription factor known to promote proliferation, is essential for spinal cord regeneration. Surprisingly, Foxm1 does not control the cell cycle length of neural progenitors but regulates their fate after division. In foxm1−/− tadpoles, we observe a reduction in the number of neurons in the regenerating spinal cord, suggesting that neuronal differentiation is necessary for the regenerative process. Altogether, our data uncover a spinal cord‐specific response to injury and reveal a new role for neuronal differentiation during regeneration.

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“…1B, 1C, dots). To test whether there is a transition between two subsequent growth modes, we followed a previously reported approach 19, 20 to determine the border separating two spatial regions within the anterior-posterior axis of the axolotl spinal cord during regeneration (see methods section). We fitted the ST and SV normograms with a two-line mathematical model, assuming two subsequent linear growths separated by a transition age (Fig.…”

Section: Resultsmentioning

confidence: 99%

Post-embryonic development and aging of the appendicular skeleton inAmbystoma mexicanum

Riquelme-Guzmán

Schuez

Böhm

et al. 2021

Preprint

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Background: The axolotl is a key model organism for studying appendicular regeneration in vertebrates. The axolotl limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop post-embryonically. In this work, we evaluated the post-embryonic development of the appendicular skeleton and its changes with aging. Results: Juvenile skeletal elements are formed mostly by SOX9+/COL1A2+ cartilage cells. Ossification of the appendicular skeleton starts when animals reach a total length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated to the ossification center and to the formation of the marrow cavity. We identified the contribution of Col1a2+ cells to bone and adipocytes. Moreover, ossification progresses with age towards the epiphyses of long bones. Even though axolotls are neotenic salamanders, ossification remains responsive to L-thyroxine, increasing the rate of bone formation. Conclusions: Bone maturation is a continuous process in axolotls that extends throughout the life span of the axolotls. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element.

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Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

Cited by 32 publications

References 52 publications

Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum

Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum

Foxm1 regulates neural progenitor fate during spinal cord regeneration

Post-embryonic development and aging of the appendicular skeleton inAmbystoma mexicanum

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