Formation of intermediate mesoderm

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Homo sapiens
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IIntermediate mesoderm gives rise to the urogenital system including the gonads and all components of the kidney, with the anterior intermediate mesoderm giving rise to the ureteric epithelium and the posterior intermediate epithelium giving rise to the metanephric mesenchyme. Intermediate mesoderm, is induced by a graded level of BMP signaling between the lateral plate mesoderm (high BMP activity) and the paraxial mesoderm (low BMP activity) (inferred from mouse embryos: James and Schultheiss 2005, reviewed by Davidson et al. 2019). Specification of the intermediate mesoderm in the anterior-posterior dimension is influenced by the caudal-rostral gradient Wnt and FGF signaling and rostral-caudal gradient retinoic acid signaling (inferred from mouse embryos: Cartry et al. 2006, reviewed by Davidson et al. 2019).
In mouse, the first observed markers of intermediate mesoderm are Osr1 and Lhx1, which are also expressed in the lateral plate mesoderm. Later, Pax2 and Pax8 are expressed specifically in the intermediate mesoderm. In mouse embryos, knockout experiments indicate that Osr1 activates Lhx1 and Pax2 (Wang et al. 2005), Lhx1 activates Pax2 (Tsang et al. 2000), and Pax2 activates Lhx1 and Osr1 (Boualia et al. 2013, Ranghini and Dressler 2015, reviewed in Marcotte et al. 2013). Foxc1 and Foxc2 produced in the paraxial mesoderm repress Lhx1 and Osr1 and thereby restrict the expansion of intermediate mesoderm (Wilm et al. 2004).
In vitro, human pluripotent stem cells can be induced to form intermediate mesoderm by treatment with a Wnt agonist (CHIR99021) followed by treatment with FGF2 and retinoic acid (Lam et al. 2014).
Literature References
PubMed ID Title Journal Year
30172050 Turning mesoderm into kidney

Davidson, AJ, Sander, V, Lewis, P, Przepiorski, A

Semin Cell Dev Biol 2019
24104595 Gene regulatory network of renal primordium development

Marcotte, M, Bouchard, M, Sharma, R

Pediatr Nephrol 2014
24357672 Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers

Morizane, R, Valerius, MT, Bonventre, JV, Lerou, PH, Freedman, BS, Lam, AQ

J Am Soc Nephrol 2014
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