The findings suggest that the non-image-forming pathway is functional long before the mainstream image-forming pathway during development.
BackgroundMost retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown.ResultsHere, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin innervating the SCN at postnatal ages, unlike most RGCs, which innervate their image-forming targets embryonically. Moreover, the appearance of ipRGC axons in the OPN coincides precisely with the onset of the pupillary light response.ConclusionsSome ipRGCs differ not only functionally but also developmentally from RGCs that mediate pattern-forming vision.
Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor Atoh7, expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore, Atoh7 is considered essential for conferring competence on progenitors to generate RGCs. Despite the importance of Atoh7 in RGC specification, we find that inhibiting apoptosis in Atoh7-deficient mice by loss of function of Bax only modestly reduces RGC numbers. Single-cell RNA sequencing of Atoh7;Bax-deficient retinas shows that RGC differentiation is delayed but that the gene expression profile of RGC precursors is grossly normal. Atoh7;Bax-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry but exhibit severe axonal guidance defects. This study reveals an essential role for Atoh7 in RGC survival and demonstrates Atoh7-dependent and Atoh7-independent mechanisms for RGC specification.
Transposition of the Ty1 element of the yeast Saccharomyces cerevisiae is temperature sensitive. We have identified a null allele of the silent information regulator gene SIR4 as a host mutant that allows for transposition at high temperature. We show that the apparent increase in transposition activity in sir4 mutant strains at high temperature is dependent on the RAD52 gene and is thus likely resulting from an increase in Ty1 cDNA recombination, rather than in IN-mediated integration. General cellular recombination is not increased at high temperature, suggesting that the increase in recombination at high temperature in sir4 mutants is specific for Ty1 cDNA. Additionally, this high-temperature Ty1 recombination was found to be dependent on functional Sir2p and Sir3p. We speculate that the increase in recombination seen in sir4 mutants at high temperature may be due to changes in chromatin structure or Ty1 interactions with chromosomal structures resulting in higher recombination rates.
36Retinal ganglion cells (RGCs), which relay visual information from the eye to the brain, 37 are the first cell type generated during retinal neurogenesis. Loss of function of the 38 transcription factor Atoh7, which is expressed in multipotent early neurogenic retinal 39 progenitor cells, leads to a selective and near complete loss of RGCs. Atoh7 has thus 40 been considered essential for conferring competence on progenitors to generate RGCs. 41However, when apoptosis is inhibited in Atoh7-deficient mice by loss of function of Bax, 42 only a modest reduction in RGC number is observed. Single-cell RNA-Seq of 43Atoh7;Bax-deficient retinas shows that RGC differentiation is delayed, but that RGC 44 precursors are grossly normal. Atoh7;Bax-deficient RGCs eventually mature, fire action 45 potentials, and incorporate into retinal circuitry, but exhibit severe axonal guidance 46 defects. This study reveals an essential role for Atoh7 in RGC survival, and 47
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