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  • Title: Pbx1 is essential for adrenal development and urogenital differentiation.
    Author: Schnabel CA, Selleri L, Cleary ML.
    Journal: Genesis; 2003 Nov; 37(3):123-30. PubMed ID: 14595835.
    Abstract:
    Pbx1 encodes a TALE (three amino acid loop extension) class homeodomain protein that participates in multimeric transcriptional complexes to regulate developmental gene expression. Previous studies demonstrate a critical role for Pbx1 as a developmental regulator whose absence results in embryonic lethality and multiple tissue and organ system abnormalities. Here we report a requirement for Pbx1 in the differentiation of urogenital organs, where Pbx1 is widely expressed in mesenchymal tissues. The complete lack of adrenal glands and formation of gonads displaying rudimentary sexual differentiation correlated with decreased cellular proliferation in Pbx1(-/-) genital ridges. Furthermore, expression of steroidogenic factor-1 (SF-1), a nuclear receptor essential for adrenal organogenesis, was reduced to minimal levels in Pbx1 mutants, indicating an upstream function for Pbx1 in adrenocortical development. Finally, loss of Pbx1 markedly reduces urogenital ridge outgrowth and results in impaired differentiation of the mesonephros and kidneys and the absence of Müllerian ducts. These findings establish a Pbx1-dependent pathway that regulates the expansion of SF-1 positive cells essential for adrenal formation and gonadal differentiation and demonstrate an early requirement for Pbx1 in urogenital development.
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