You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.

Title: Tissue absence initiates regeneration through Follistatin-mediated inhibition of Activin signaling}
Article:
Abstract:
Regeneration is widespread, but mechanisms that activate regeneration remain mysterious. Planarians are capable of whole-body regeneration and mount distinct molecular responses to wounds that result in tissue absence and those that do not. A major question is how these distinct responses are activated. We describe a follistatin homolog( Smed-follistatin) required for planarian regeneration. Smed-follistatin inhibition blocks responses to tissue absence but does not prevent normal tissue turnover. Two activin homologs( Smed-activin-1 and Smed-activin-2) are required for the Smed-follistatin phenotype. Finally, Smed-follistatin is wound-induced and expressed at higher levels following injuries that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed-Activin proteins to trigger regeneration specifically following injuries involving tissue absence and identify a mechanism critical for regeneration initiation, a process important across the animal kingdom.
Introduction:
Regeneration occurs in widespread contexts and species. Invertebrates such as Hydra are capable of whole-animal regeneration from tissue fragments, and many vertebrates can regenerate appendages or repair damaged organs( Sánchez Alvarado, 2000). Despite this widespread relevance, the central mechanisms that drive regeneration are poorly understood. Planarians are flatworms capable of regeneration following an almost limitless variety of injuries and have emerged as a powerful model for exploring the molecular underpinnings of regeneration( Newmark and Sánchez Alvarado, 2002). New tissues are formed at planarian wound sites in a process called blastema formation, and pre-existing tissues are reorganized after amputation to accommodate reduced animal size and further generate missing tissues( Morgan, 1901; Reddien and Sánchez Alvarado, 2004). The source of regenerated tissue in planarians is a population of adult dividing cells called neoblasts( Reddien and Sánchez Alvarado, 2004), which include pluripotent stem cells called clonogenic neoblasts( cNeoblasts)( Wagner et al., 2011). Neoblasts are the only somatic cycling cells in adult animals and can be specifically ablated by gamma irradiation, allowing for dissection of the requirements for neoblasts in regenerative processes( Reddien and Sánchez Alvarado, 2004). Recent work has described the earliest molecular and cellular events that occur following injury( Pellettieri et al., 2010; Wenemoser and Reddien, 2010; Sandmann et al., 2011; Wenemoser et al., 2012). One finding to emerge from this work is that animals initiate distinct cellular and molecular responses to ‘major injuries’ that remove significant amounts of tissue( e. g., head amputation) and to ‘simple injuries’ that require only minimal healing for repair( wounds that do not elicit blastema formation, such as punctures or incisions). Following simple injury, for example, animals display an increase in mitotic numbers 6 hr after injury before returning to baseline levels( Wenemoser and Reddien, 2010), and expression of numerous wound-induced genes becomes undetectable by 24 hr after injury( Wenemoser et al., 2012). Following a major injury, these same initial responses are observed, but subsequent responses are also activated: the 6 hr increase in mitotic numbers is followed by a second increase 48 hr after amputation( Wenemoser and Reddien, 2010), and wound-induced gene expression persists beyond 24 hr and is refined over several days( Wenemoser et al., 2012). These responses are referred to as the ‘missing-tissue response’( Wenemoser and Reddien, 2010; Wenemoser et al., 2012). How animals distinguish between injuries involving varying amounts of tissue loss and regulate these distinct wound response programs remains unknown. We identified Smed-follistatin as required for molecular and cellular ‘missing-tissue’ responses during regeneration. Specifically, Follistatin-mediated inhibition of Activin signaling is required for regeneration to occur, with Smed-follistatin expression at wounds controlled by the extent of tissue absence following injury. These results suggest a mechanism by which regenerative responses can be initiated.
Discussion:
All long-living animals face the prospect of injury and require regenerative mechanisms. Planarians are an exceptional example of the regenerative potential of animals. Distinct cellular and molecular programs for responding to simple injury vs missing tissue exist in planarians. In the case of injuries involving substantial missing tissue, animals mount unique mitotic and apoptotic responses and produce an extended program of wound-induced gene expression( Pellettieri et al., 2010; Wenemoser and Reddien, 2010; Wenemoser et al., 2012). These events represent the earliest described divergent behaviors following major injuries requiring regeneration vs simple injuries requiring only wound healing. A central question has therefore become how these distinct responses are mediated. We identified a gene encoding a homolog of the TGF-β inhibitor, follistatin, that is required for regeneration and for regeneration-specific cellular and molecular responses to injury. Our data suggest that inhibition of Activin signaling by Fst is required for initiating a regenerative response at wounds following major injury. Finally, fst is wound-induced, with the level of fst expression persisting at high levels longer following a major injury than following a simple injury. We propose that wound-induced fst expression allows for regenerative responses to be initiated specifically as a consequence of tissue absence. fst is the first gene known to be required for regeneration-specific responses in planarians. Not all missing-tissue responses are abolished following fst inhibition, however. For example, neoblast migration to amputation sites occurred normally in fst( RNAi) animals, despite the absence of a normal proliferative response. Similarly, although expression of act-1 and act-2 are required for the fst( RNAi) phenotype, inhibition of activin expression in the absence of amputation does not affect homeostatic tissue turnover or induce a regeneration-like state, demonstrating that the suppression of Activin alone is not sufficient to induce missing-tissue responses. Therefore, some aspects of the missing-tissue response to injury require an as yet unknown ‘missing-tissue’ signal or signals that operate independently of fst and Activin signaling. Identifying and characterizing these processes will be important for understanding how the decision to mount a regenerative response occurs. Our findings describe a system in which suppression of Activin signaling is required for regeneration. The possibility therefore exists that Activin signaling may serve similar functions in other organisms. Indeed, TGF-β signaling has been implicated as a negative regulator of regeneration in a variety of contexts, including following partial hepatectomy( Russell et al., 1988; Kogure et al., 1995; Romero-Gallo et al., 2005), in embryonic chick retinas( Sakami et al., 2008), in renal regeneration following ischemia/reperfusion injuries( Kojima et al., 2001), and for mouse skeletal muscle regeneration( Zhu et al., 2011). Given the relevance of these systems to human medicine, it will be important to investigate to what extent regenerative regimes recapitulate the mechanisms observed in planarians. Interestingly, a number of systems use TGF-β signaling to promote rather than suppress regeneration: TGF-β signaling is involved in axolotl limb and Xenopus tail regeneration( Lévesque et al., 2007; Ho and Whitman, 2008), activin expression can be induced by wounding and exogenous TGF-β can speed healing in mammals( Mustoe et al., 1987; Hübner et al., 1996; Sulyok et al., 2004), TGF-β signaling can promote regeneration following mouse ear hole-punching( Liu et al., 2011), and wound-induced activin promotes cell proliferation and migration following zebrafish fin amputation( Jaźwińska et al., 2007). Despite these contextual differences, TGF-β signaling plays a major role in many forms of regeneration studied. Therefore, uncovering ‘missing-tissue’ signals in planarians, describing how these signals interact with Activin signaling, and identifying the key factors regulated by these signals will inform a broad understanding of core regenerative mechanisms.
Most animals can respond to injury with some form of tissue regeneration . In mammals , this is limited to wound healing , whereas other vertebrates—such as salamanders and zebrafish—can regenerate parts of internal organs and even entire appendages . The planarian , a flatworm , is even more remarkable , being able to regenerate its head or tail following amputation , and even a whole animal from just a small body fragment . This is particularly impressive given that planarians have a complex internal anatomy , which includes muscles , intestines , a system similar to kidneys , and a central nervous system with a brain . How is such regeneration accomplished ? Why are planarians able to regenerate their bodies so extensively , whereas humans cannot ? To what extent are the mechanisms of planarian regeneration common to other animals ? These questions have driven the study of planarian regeneration for more than a century , but it is only in recent years that the tools needed to address these questions at the molecular level have become available . Planarian regeneration proceeds over several days and involves multiple processes , including gene expression , cell division and cell death . Importantly , it has recently been shown that planarians activate different responses depending on whether an injury results in significant tissue loss—and therefore requires regeneration for repair—or if simple wound healing will be sufficient . The mechanisms behind these different responses to injury have , however , remained a mystery . Now , Gaviño et al . have identified a key mechanism in the initiation of regeneration following tissue loss . This is centered on the gene follistatin , which is expressed following wounding . When genetic techniques are used to disrupt the expression of follistatin , regeneration is completely blocked . However , the animal’s ability to routinely replace old cells via a stem-cell mediated mechanism is unaffected . This indicates that follistatin is specifically required for the replacement of cells lost through injury . Gaviño et al . further demonstrate that the protein encoded by follistatin likely initiates tissue regeneration upon substantial tissue loss through inhibition of proteins called Activins . Activin and Follistatin proteins are broadly conserved in evolution , and are also expressed in mammals , raising the possibility that similar molecular circuits may govern regenerative responses in many species .