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Single-cell profiling of penta- and tetradactyl mouse limb buds identifies early mesenchymal progenitors required to specify digit numbers and asymmetry

ABSTRACT: Single-cell profiling of penta- and tetradactyl mouse limb buds identifies early mesenchymal progenitors required to specify digit numbers and asymmetry

PROVIDER: PRJNA1109330 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28966700.fastq.gz	Fastqsanger.gz
	SRR28966701.fastq.gz	Fastqsanger.gz
	SRR28966702.fastq.gz	Fastqsanger.gz
	SRR28966703.fastq.gz	Fastqsanger.gz
	SRR28966704.fastq.gz	Fastqsanger.gz

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Single-cell profiling of penta- and tetradactyl mouse limb buds identifies early mesenchymal progenitors required to specify digit numbers and asymmetry

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Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.

Project description:The cellular interactions controlling digit numbers and identities have remained largely elusive. Here, we leverage the anterior digit and identity loss in Grem1 tetradactyl mouse limb buds to identify early specified limb bud mesenchymal progenitor (LMP) populations whose size and distribution is governed by spatial modulation of BMP activity and SHH signaling. Distal-autopodial LMPs (dLMP) express signature genes required for autopod and digit development, and alterations affecting the dLMP population size prefigure the changes in digit numbers that characterize specific congenital malformations. A second, peripheral LMP (pLMP) population is anteriorly biased and reduction/loss of its asymmetric distribution underlies the loss of middle digit asymmetry and identities in Grem1 tetradactyl and pig limb buds. pLMPs depend on BMP activity, while dLMPs require GREM1-mediated BMP antagonism. Taken together, the spatial alterations in GREM1 antagonism in mouse mutant and evolutionarily diversified pig limb buds tunes BMP activity, which impacts dLMP and pLMP populations in an opposing manner.

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Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general. A large-scale analysis of gene expression of 3 different parts of autopods in Myotis ricketti using digital gene expression tag profiling approach.

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