During retinal development, different types of neurons arise in a conserved temporal sequence from multipotent cycling retinal progenitor cells. But do the progenitor cells decide the fate of their daughter cells and pass on this decision via determinants or is the fate of the daughter cells determined postmitotically? Constance Cepko and co-workers () address this question using a conditional allele (N1-CKO) to remove the cell fate regulator Notch1 in newly postmitotic mouse retinal cells. Nearly all newly postmitotic N1-CKO cells become rod photoreceptors, the researchers report, whereas wild-type cells adopt several cell fates: photoreceptors, bipolar cells and Müller glia. Notably, single-cell expression profiling indicates that several direct targets of Notch signalling are differentially expressed in wild-type and N1-CKO cells transitioning from progenitor to differentiated states. These findings suggest that newly postmitotic retinal cells need Notch to escape the photoreceptor fate, and thus may have some degree of plasticity with respect to cell fate.
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