Early Development of the Gonads: Origin and Differentiation of the Somatic Cells of the Genital Ridges

Abstract

The earliest manifestation of gonadogenesis in vertebrates is the formation of the genital ridges. The genital ridges form through the transformation of monolayer coelomic epithelium into a cluster of somatic cells. This process depends on increased proliferation of coelomic epithelium and disintegration of its basement membrane, which is foreshadowed by the expression of series of regulatory genes. The earliest expressed gene is Gata4, followed by Sf1, Lhx9, Emx2, and Cbx2. The early genital ridge is a mass of somatic SF1-positive cells (gonadal precursor cells) that derive from proliferating coelomic epithelium. Primordial germ cells (PGCs) immigrate to the coelomic epithelium even in the absence of genital ridges, e.g., in mouse null mutants for Gata4. And conversely, the PGCs are not required for the formation of the genital ridges. After reaching genital ridges, the PGCs become enclosed by somatic cells derived from coelomic epithelium. Subsequently, the expression of sex-determining genes begins and the bipotential gonads differentiate into either testes or ovaries. Gonadal precursor cells, derived from coelomic epithelium, give rise to the somatic supporting cells such as Sertoli cells, follicular cells, and probably also peritubular myoid and steroidogenic cells.

Connection between seminiferous tubules and epididymal duct is originally induced before sex differentiation in a sex‐independent manner

“…Because of the unpredicted findings that the adjacent localization of the Ad4BP/SF‐1 gonadal cells and MT was observed before the sex differentiation in the gonad, seq‐IHC was performed on the embryo at 9.5 dpc when several genes that are necessary for the formation of the undifferentiated gonad start to be expressed . Ad4BP/SF‐1, one of such genes, was detected at coelomic epithelial cells, especially in the region with underlying Pax2‐positive MT (Figure A,B).…”

“…The developmental process of the testis and epididymis in mice has been well investigated. Gonadal formation occurs in the ventromedial region of a mesonephros at 9.5 days post coitum (dpc) as a genital ridge (GR) . Some genes were identified as regulators of the formation of the GR.…”

Mapping molecular pathways for embryonic Sertoli cells derivation based on differentiation model of mouse embryonic stem cells

“…Some coelomic epithelial somatic cells went through epithelial-mesenchymal transition (EMT) and developed into nuclear receptor subfamily 5, group A, member 1 (NR5A1, i.e., SF1)-positive cells, as the main precursor cells of Sertoli cells. In this phase, some factors were involved including Wilms tumor 1 homolog (Wt1), GATA binding protein 4 (Gata4), LIM homeobox protein 9 (Lhx9), empty spircles homeobox 2 (Emx2), transcription factor 21 (Pod1), tripartite motifcontaining 28 (Tif1β), nuclear receptor coactivator 2 (Tif2), insulin receptor (Insr), chromobox 2 (Cbx2), sine oculis-related homeobox 1/4 (Six1/4), zinc finger protein multitype 2 (Fog2), mitogen-activated protein kinase 4 (Map3k4), growth arrest, and DNAdamage-inducible 45 gamma (Gadd45g) [6][7][8][9][10][11][12][13][14][15]. In mice, these SF1-positive precursor cells (SPCs) ingressed into bipotential gonads and became SF1-positive gonadal precursor cells (SGPCs, i.e., pre-Sertoli cells) in 11.2-11.4 day post coitum (dpc).…”

“…The main complications of exploring the deriving mechanism of Sertoli cells are as follows: the cells have a great variety in genital ridges and coelomic epithelium, the relevant factors have complicated interaction, the target genes are hard to manipulate in vivo environment, and so on [6,14,18,22,23]. Consequently, recently, some studies provided molecular mechanism through inducing Sertoli-like cells from embryonic stem cells by retiotic acid (RA) treatment, reducing the size of cultured ESC colonies, and some other factors [24,25].…”

Matrix metalloproteinase-dependent regulation of extracellular matrix shapes the structure of sexually differentiating mouse gonads

“…Although this processes has been well studied in mice, the molecular and 71 cellular machinery governing the development of testes and ovaries is very complex and still 72 requires further studies. Gonad primordia, termed genital ridges, appear in mice soon before 73 10.5 th day of embryonic life (E10.5) (Hu et al, 2013; reviewed by Piprek et al, 2016). 74…”