It is widely accepted that the process of retinal cell fate determination is under tight transcriptional control mediated by a combinatorial code of transcription factors. However, the exact repertoire of factors necessary for the genesis of each retinal cell type remains to be fully defined. Here we show that the HMG-box transcription factor, Sox9, is expressed in multipotent mouse retinal progenitor cells throughout retinogenesis. We also find that Sox9 is downregulated in differentiating neuronal populations, yet expression in Mü ller glial cells persists into adulthood. Furthermore, by employing a conditional knockout approach, we show that Sox9 is essential for the differentiation and/or survival of postnatal Müller glial cells. J. Comp. Neurol. 510: 237–250, 2008.© 2008 Wiley-Liss, Inc.