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

Singh, Neha; Singh, Domdatt; Bhide, Anshul; Sharma, Richa; Sahoo, Sarthak; Jolly, Mohit Kumar; Modi, Deepak

doi:10.1016/j.yexcr.2022.113108

Cited by 8 publications

(24 citation statements)

References 66 publications

(122 reference statements)

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“…LIM-homeodomain gene 2 ( LHX2 ), known to be an important transcription factor, belongs to the subfamily of homeobox genes which are specifically characterized by N terminal two tandem cysteine-rich zinc finger LIM domains for protein binding (cofactors) and a C terminal one homeodomain for DNA binding [ 3 , 4 ]. Numerous studies have reported that LHX2 is fundamental to embryonic development; it is involved in skin, nervous system, brain, eye and gonad development and hematopoiesis [ 5 ]. During the process of embryonic development, LHX2 exhibits multifarious phase- and cell type-specific functions by controlling signal transduction, cell fate determination and cell differentiation [ 3 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

Chen

et al. 2022

Genes

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LHX2 dysregulations have been found to present in cancers, but the function of LHX2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we report that LHX2 was upregulated in ESCC tissues in comparison to the LHX2 levels in adjacent normal tissues. Loss- and gain-of-function experiments demonstrated that the knockdown of LHX2 markedly inhibited ESCC cells’ proliferation, migration, invasion, tumor growth and metastasis, whereas the overexpression of LHX2 had the opposite effects. A mechanistic investigation revealed that LHX2 bound to the promoter of SERPINE2 gene and transcriptionally regulated the expression of SERPINE2. Collectively, LHX2 facilitates ESCC tumor progression, and it could be a potential therapeutic target for ESCC.

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Section: Introductionmentioning

confidence: 99%

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

Chen

et al. 2022

Genes

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“…However, in the developing gonads, Lhx9 is expressed in somatic cells [51] while Lhx2 is in the germ cells suggesting their divergent role in gonad development. Indeed, in the Lhx9 knockouts, the gonad development is arrested before the onset of sex determination; the ovary [26] and the testis (present study) develop normally in absence of Lhx2 . Also, the specification of germ cells and Sertoli cells is unaltered in Lhx2-/- testis, and neither the number of germ cells and Sertoli cells are compromised in Lhx2-/- XY gonads.…”

Section: Discussionmentioning

confidence: 74%

“…Lhx2 is involved in anterior/posterior and proximal/distal pattern formation and morphogenesis, neuron migration, and limb bud morphogenesis in many species [25,54]. Since these processes are also enriched in the testis (present study) and ovary [26] of Lhx2 knockouts, it is tempting to propose that there would be a core transcriptome regulated by Lhx2 which has overlapping functions irrespective of the tissue.…”

Section: Discussionmentioning

confidence: 80%

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LHX2 in germ cells control tubular organization in the developing mouse testis

Singh

Bhide

et al. 2022

Preprint

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In the gonads of mammalian XY embryos, the organization of cords is the hallmark of testis development. This organization is thought to be controlled by interactions of the Sertoli cells, endothelial and interstitial cells with little or no role of germ cells. Challenging this notion, herein we show that the germ cells play an active role in the organization of the testicular tubules. We observed that the LIM-homeobox gene, Lhx2 is expressed in the germ cells of the developing testis between E12.5-E15.5. In Lhx2 knockout- fetal testis there was altered expression of several genes not just in germ cells but also in the supporting (Sertoli) cells, endothelial cells, and interstitial cells. Further, loss of Lhx2 led to disrupted endothelial cell migration and expansion of interstitial cells in the XY gonads. The cords in the developing testis of Lhx2 knockout embryos are disorganized with a disrupted basement membrane. Together, our results show an important role of Lhx2 in testicular development and imply the involvement of germ cells in the tubular organization of the differentiating testis.

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“…Beyond granulosa cells, the functions of other ovarian cell populations such as NR2F2+ interstitium or germ cells cannot be ignored. For instance, Lhx2 gene in germ cells is involved in repression of endothelial cell migration in the mouse developing ovary ( Singh et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Becoming female: Ovarian differentiation from an evolutionary perspective

Nicol

Estermann

Yao

et al. 2022

Front. Cell Dev. Biol.

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Differentiation of the bipotential gonadal primordium into ovaries and testes is a common process among vertebrate species. While vertebrate ovaries eventually share the same functions of producing oocytes and estrogens, ovarian differentiation relies on different morphogenetic, cellular, and molecular cues depending on species. The aim of this review is to highlight the conserved and divergent features of ovarian differentiation through an evolutionary perspective. From teleosts to mammals, each clade or species has a different story to tell. For this purpose, this review focuses on three specific aspects of ovarian differentiation: ovarian morphogenesis, the evolution of the role of estrogens on ovarian differentiation and the molecular pathways involved in granulosa cell determination and maintenance.

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

Cited by 8 publications

References 66 publications

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2

LHX2 in germ cells control tubular organization in the developing mouse testis

Becoming female: Ovarian differentiation from an evolutionary perspective

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