{'fraction_non_alphanumeric': 0.020036429872495445, 'fraction_numerical': 0.0, 'mean_word_length': 5.488188976377953, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Multiple mechanisms contribute to the avoidance of avian epidermis by sensory axons.

In birds, sensory innervation of skin is restricted to dermis, with few axons penetrating into the epidermis. This pattern of innervation is maintained in vitro, where sensory neurites avoid explants of epidermis but grow readily on dermis. We have used this coculture paradigm to investigate the mechanisms that impede innervation of avian epidermis. The lack of epidermal innervation in birds has been attributed to diffusible chondroitin sulfate proteoglycans (CSPGs) secreted by the epidermis, although direct experimental evidence is weak. We found that elimination of CSPG function with either chondroitinase or neutralizing antibodies did not promote growth of DRG neurites onto epidermis in vitro, indicating that CSPGs alone are not responsible for preventing epidermal innervation. Moreover, the failure of sensory neurites to invade epidermis is not due exclusively to soluble chemorepulsive factors, since sensory neurites also avoid dead epidermis. This inhibition can be overridden, however, by coating epidermis with the growth-promoting molecule laminin, but only if the tissue is killed first. Epidermal innervation of laminin-coated epidermis is even more robust when CSPGs are also eliminated. Thus, the absence of growth-promoting or permissive molecules, such as laminin, may contribute to the failure of sensory neurites to invade avian epidermis. Together these results show that the inhibitory character of avian epidermis is complex. Cell- or matrix-associated CSPGs clearly contribute to the inhibition, but are not solely responsible.