_Toxins_**2010**, \(2\), 367-381; doi:10.3390/toxins2040367  
_toxins_  
**ISSN 2072-6651**  
www.mdpi.com/journal/toxins  
_Review_  
**Role of the Osmotic Stress Regulatory Pathway in**  
**Morphogenesis and Secondary Metabolism in Filamentous Fungi**  
**[PERSON] 1, [PERSON] 2 and [PERSON] 1,****  
Footnote  
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11: footnotemark:  
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nature, it must be capable of adapting quickly to any particular environment it may find itself in. Even when acclimated to their particular niche, perturbations can occur from time to time in the surrounding environment either as a result of natural causes (_i.e._, drought) or man-made causes (_i.e._, modern agriculture). To adapt to such environmental changes fungi must continually adjust their physiology in order to enhance survival. At the molecular level, fungi possess complex signal transduction pathways that allow the fungus to respond appropriately to alterations in external stimuli. These stimuli can include biotic stress, and abiotic stresses such as changes in temperature, pH, nutrient availability, oxidative stress and osmotic stress. In this report we will be focusing on the role that osmotic stress plays in the growth and development of filamentous fungi and the molecular mechanisms that control the fungus' response to alterations in osmotic pressure. Many of the studies that first identified genes involved in the molecular regulation of cellular responses to osmotic pressure were performed in the yeast _Saccharomyces cerevisiae_ (reviewed in [1]). These included the identification of MAP kinase signaling pathways and the high osmolarity glycerol (HOG) pathway involved in response to osmotic pressure [2]. In addition to providing information gleaned from studies using _S. cerevisiae_, we will also focus on research involving filamentous fungi, particularly of the genus Aspergillus. _A. nidulans_ has been used extensively as a model fungus for the study of the molecular genetics of responses to osmotic stress due in large part to the availability of a vast number of genetic markers and a sexual stage that allows for genetic recombination studies [3,4]. _A. nidulans_ also produces the mycotoxin sterigmatocystin, which is synthesized through the same conserved pathway that leads to production of aflatoxin in other Aspergillus. Both compounds are potent carcinogenic mycotoxins. In addition to A. nidulans, the genus _Aspergillus_ includes a number of species that are of great importance both economically and medically. For example, the agriculturally important aflatoxin-producing species _A. flavus_ and _A. parasiticus_[5]; _A. oryzae_ and _A. niger_ as industrially important sources of enzymes [6,7]; and medically important species such as the causal agent of human aspergillosis, the gliotoxin-producer _A. fumigatus_[8]. A number of studies have reported on the effects of osmotic stress on _Aspergillus_ spp. as influenced by water content, water activity (Aw), and solute concentrations. [PERSON] _et al._[9] reported on the effect of moisture (measured as percent moisture content or osmotic pressure) and substrate variation in developing cottonseed and corn. They found that osmotic pressure and other factors such as oil and starch content of seeds determine the physiological responses of _A. parasiticus_. Maximum accumulation of aflatoxin was observed in corn kernels and cottonseed that were inoculated at 52 and 70% moisture content, respectively. A water availability in the 600 kPa range of osmotic pressure provided optimum conditions for _A. parasiticus_ development in corn kernels. Osmotic stress has also been shown to be a critical factor in enzyme production, relevant in industrial fermentations that utilize aspergillus. It was found that increased osmotic pressure as determined by NaCl concentration resulted in increased production and secretion of glucose oxidase during fermentation by _A. niger_[10]. [PERSON] _et al._[11] found that glucoamylase activity by _A.