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Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

Singh, N and Singh, D and Bhide, A and Sharma, R and Sahoo, S and Jolly, MK and Modi, D (2022) Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary. In: Experimental Cell Research, 415 (1).

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Official URL: https://doi.org/10.1016/j.yexcr.2022.113108


Abstract LIM-homeobox genes play multiple roles in developmental processes, but their roles in gonad development are not completely understood. Herein, we report that Lhx2, Ils2, Lmx1a, and Lmx1b are expressed in a sexually dimorphic manner in mouse, rat, and human gonads during sex determination. Amongst these, Lhx2 has female biased expression in the developing gonads of species with environmental and genetic modes of sex determination. Single-cell RNAseq analysis revealed that Lhx2 is exclusively expressed in the germ cells of the developing mouse ovaries. To elucidate the roles of Lhx2 in the germ cells, we analyzed the phenotypes of Lhx2 knockout XX gonads. While the gonads developed appropriately in Lhx2 knockout mice and the somatic cells were correctly specified in the developing ovaries, transcriptome analysis revealed enrichment of genes in the angiogenesis pathway. There was an elevated expression of several pro-angiogenic factors in the Lhx2 knockout ovaries. The elevated expression of pro-angiogenic factors was associated with an increase in numbers of endothelial cells in the Lhx2−/− ovaries at E13.5. Gonad recombination assays revealed that the increased numbers of endothelial cells in the XX gonads in absence of Lhx2 was due to ectopic migration of endothelial cells in a cell non-autonomous manner. We also found that, there was increased expression of several endothelial cell-enriched male-biased genes in Lhx2 knockout ovaries. Also, in absence of Lhx2, the migrated endothelial cells formed an angiogenic network similar to that of the wild type testis, although the coelomic blood vessel did not form. Together, our results suggest that Lhx2 in the germ cells is required to suppress vascularization in the developing ovary. These results suggest a need to explore the roles of germ cells in the control of vascularization in developing gonads.

Item Type: Journal Article
Publication: Experimental Cell Research
Publisher: Elsevier Inc.
Additional Information: The copyright for this article belongs to the Authors.
Keywords: angiogenic factor; cadherin; complementary DNA; dazl protein; deoxyribonuclease I; estrogen receptor; ils2 protein; lmx1a protein; lmx1b protein; tamoxifen; transcription factor; transcription factor LIM homeobox; transcriptome; unclassified drug; vasculotropin receptor 1; vasculotropin receptor 2; Lhx2 protein, mouse; Lhx2 protein, rat; LIM homeodomain protein; transcription factor, adult; angiogenesis; animal cell; animal experiment; Article; blood vessel; cell migration; controlled study; differential expression analysis; endothelium cell; environmental factor; female; gene knockout; genetic analysis; germ cell; gonad; gonad development; human; karyotype 46,XX; male; Monodelphis domestica; mouse; nonhuman; ovary development; phenotypic variation; protein expression; rat; real time polymerase chain reaction; RNA extraction; sex determination; sex determination process; sex transformation; single cell RNA seq; somatic cell; testis; vascularization; animal; endothelium cell; gene expression regulation; genetics; germ cell; metabolism; ovary; sex differentiation, Animals; Endothelial Cells; Female; Gene Expression Regulation, Developmental; Germ Cells; Gonads; LIM-Homeodomain Proteins; Male; Mice; Ovary; Rats; Sex Differentiation; Testis; Transcription Factors
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 22 Jun 2022 05:16
Last Modified: 22 Jun 2022 05:16
URI: https://eprints.iisc.ac.in/id/eprint/73612

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