Canids display a wide diversity of social systems, from solitary to pairs to packs, and hence they have been extensively used as model systems to understand social dynamics in natural systems.Among canids, the dog can show various levels of social organization due to the influence of humans on their lives. Though the dog is known as man's best friend and has been studied extensively as a pet, studies on the natural history, ecology and behaviour of dogs in a natural habitat are rare. Here we report results of an extensive population-level study conducted through one-time censuses in urban India to understand the ecoethology of free-ranging dogs. We built a model to test if the observed groups could have been formed through random associations while foraging. Our modeling results suggest that the dogs, like all efficient scavengers, tend to forage singly but also form random uncorrelated groups. A closer inspection of the group compositions however reveals that the foraging associations are non-random events. The tendency of adults to associate with the opposite sex in the mating season and of juveniles to stay close to adults in the non-mating season drives the population towards aggregation, in spite of the apparently random nature of the group size distribution. Hence we conclude that to be or not to be social is a matter of choice for the free-ranging dogs, and not a matter of chance.

SummaryUpon injury, Müller glia cells of the zebrafish retina reprogram themselves to progenitor cells with stem cell characteristics. This necessity for retina regeneration is often compromised in mammals. We explored the significance of developmentally inevitable Sonic hedgehog signaling and found its necessity in MG reprogramming during retina regeneration. We report on stringent translational regulation of sonic hedgehog, smoothened, and patched1 by let-7 microRNA, which is regulated by Lin28a, in Müller glia (MG)-derived progenitor cells (MGPCs). We also show Shh-signaling-mediated induction of Ascl1 in mouse and zebrafish retina. Moreover, Shh-signaling-dependent regulation of matrix metalloproteinase9, in turn, regulates Shha levels and genes essential for retina regeneration, such as lin28a, zic2b, and foxn4. These observations were further confirmed through whole-retina RNA-sequencing (RNA-seq) analysis. This mechanistic gene expression network could lead to a better understanding of retina regeneration and, consequently, aid in designing strategies for therapeutic intervention in human retinal diseases.

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SummaryHistone deacetylases (Hdacs) play significant roles in cellular homeostasis and tissue differentiation. Hdacs are well characterized in various systems for their physiological and epigenetic relevance. However, their significance during retina regeneration remains unclear. Here we show that inhibition of Hdac1 causes a decline in regenerative ability, and injury-dependent regulation of hdacs is essential for regulating regeneration-associated genes like ascl1a, lin28a, and repressors like her4.1 at the injury site. We show selective seclusion of Hdac1 from the proliferating Müller glia-derived progenitor cells (MGPCs) and its upregulation in the neighboring cells. Hdacs negatively regulate her4.1, which also represses lin28a and essential cytokines to control MGPCs proliferation. Interestingly, Hdacs' inhibition reversibly blocks regeneration through the repression of critical cytokines and other regeneration-specific genes, which is also revealed by whole-retina RNA sequence analysis. Our study shows mechanistic understanding of the Hdac pathway during zebrafish retina regeneration.

Octamer-binding transcription factor 4 (Oct4, also known as Pou5F3) is an essential pluripotency-inducing factor, governing a plethora of biological functions during cellular reprogramming. Retina regeneration in zebrafish involves reprogramming of Müller glia (MG) into a proliferating population of progenitors (MGPCs) with stem cell–like characteristics, along with up-regulation of pluripotency-inducing factors. However, the significance of Oct4 during retina regeneration remains elusive. In this study, we show an early panretinal induction of Oct4, which is essential for MG reprogramming through the regulation of several regeneration-associated factors such as Ascl1a, Lin28a, Sox2, Zeb, E-cadherin, and various miRNAs, namely, let-7a, miR-200a/miR-200b, and miR-143/miR-145. We also show the crucial roles played by Oct4 during cell cycle exit of MGPCs in collaboration with members of nucleosome remodeling and deacetylase complex such as Hdac1. Notably, Oct4 regulates Tgf-β signaling negatively during MG reprogramming, and positively to cause cycle exit of MGPCs. Our study reveals unique mechanistic involvement of Oct4, during MG reprogramming and cell cycle exit in zebrafish, which may also account for the inefficient retina regeneration in mammals.